| Background and ObjectiveKidney stones are one of the most common conditions in urology,with a considerably high prevalence and recurrence rate in China.The large number of patients have become serious social and medical burdens,and they also give severe challenges to clinical and scientific workers.In previous studies,we found out the public's cognition and health needs of kidney stone disease through the analysis of Internet big data,among which the drug prevention and treatment of kidney stoneswas a hot topic of public concern.Therefore,how to better treat kidney stones and prevent stones formation and recurrence has become a difficult problem that needs to be urgently addressed in medical research.Currently,there are many problems in the research of kidney stones,one of which is the lack of accurate analysis methods.The development of computers and various software provides a new way to study the interaction between the atomic and molecular scales.Compared with traditional experiments,calculations and simulations carried out on computers can realize the study of drug action mechanisms at a more microscopic level,and the accuracy and repeatability of the results are satisfactory.Based on this,the first part of this research,using first principles,studied the basic problems of calcium(Ca)adsorption position,adsorption method,and adsorption energy on the surface of resveratrol(C14H12O3),trying to expound the the mechanism of resveratrol inhibiting calcium oxalate stone formation from the microstructure.On the basis of traditional experience and scientific hypothesis,network pharmacology extracts drug components,targets,genes,pathways,diseases and other key elements from experimental data or literature and database,and takes these key elements as nodes to simulate the construction of molecular association network model by calculating the relationship between nodes,so as to explore the nature of life activities and the mechanism of drug body interaction.It provides a new method for evaluating the effects of drugs and finding biological targets and molecular mechanisms.At present,there is no systematic study of resveratrol(RSV)in the prevention and treatment of calcium oxalate nephrolithiasis at home and abroad.Only a few in vitro experiments have initially shown that RSV has the potential to inhibit the formation of stones,but its mechanism is still unclear.In the second part of this study,we will screen out the potential targets of resveratrol against renal calculi,and predict its biological process and pathway.A single calculation simulation analysis cannot indicate the up-downregulation of drug to target expression,nor does it take into account the difference in drug-target-disease interaction.Therefore,the analysis results may deviate from the actual effect of drugs in the body.Therefore,it is necessary to systematically verify the experimental results at the cellular and animal levels,,which will provide a reliable basis for the prediction results of the calculation and simulation.In the third part of this research,we will focus on the cell and animal research on the prevention and treatment of calcium oxalate nephrolithiasis with resveratrol based on the previous two parts of research.Epidemiological studies have found that the prevalence of kidney stones can be significantly reduced in people who drink red wine for a long time,which may be related to resveratrol,the main active ingredient in glucose wine.Resveratrol(RSV)is a natural polyphenolic compound with a wide range of biological effects such as antioxidant,anti-cancer,neuroprotection and immune regulation.Studies have shown that supersaturated calcium oxalate crystals can induce oxidative stress injury in the kidney,resulting in changes in the membrane structure and function of renal tubular epithelial cells,thus promoting the adhesion and aggregation of crystals.The adhesion of crystals will continuously stimulate the kidney,feedback to generate more active oxygen,forming a vicious cycle,and eventually leading to the growth of stones.Therefore,oxidative stress damage to the kidney is considered to be an important mechanism for the formation of stones,and inhibition of renal injury caused by calcium oxalate crystals will help prevent the formation of kidney stones.Resveratrol can alleviate the oxidative stress injury of the kidney induced by hydrogen peroxide and high sugar.The mechanism may be that resveratrol activates the silent information regulator 1(SIRT1),prompting it to bind to the forkhead box protein O3a(FOXO3a),thereby regulating its transcriptional activity,increasing the content of antioxidant enzymes,and reducing the production of reactive oxygen species.So,can resveratrol inhibit the oxidative stress response of the kidney induced by calcium oxalate crystals,reduce kidney damage,reduce the production of osteopontin and other stone-promoting factors,and ultimately inhibit the formation of kidney stonesby targeting SIRT1/FOXO3a?At present,there is no relevant systematic research at home and abroad.This part of the study aims to provide valuable theoretical basis and experimental basis for resveratrol in preventing and treating calcium oxalate stones through in vitro and vivo experiments.Methods1.First principles study on the absorption of Ca on resveratrol sur;face1.1 The adsorption energy analysis of Ca adsorption on C14H12O3Firstly,the structural formula of resveratrol was obtained,and the structure of C14H12O3was optimized to obtain the most stable molecular conformation.According to the molecular structure of resveratrol,five sites were selected as the initial positions for calculating the adsorption energy of Ca toC14H12O3,and the adsorption energy was compared.1.2 Stable conformation of the adsorption systemIn order to further verify the stable conformation of the adsorption system,we will describe the changes in the structure of C14H12O3 after Ca adsorption.1.3 Electronic structure of Ca adsorbed on C14H12O3SurfaceThe charge density difference diagram was drawn to show the charge density redistribution before and after Ca adsorption.1.4 Comparison of the adsorption energy of Ca on C14H12O3 and C2H2O4By constructing a stable adsorption system and calculating the adsorption energy,the adsorption of Ca on C14H12O3 and C2H2O4 on Ca were compared.2.Network pharmacology study on mechanism of resveratrol against kidneystones2.1 Obtain the chemical structure,molecular and pharmacological properties of resveratrolThe key words "resveratrol" were searched in PubChem database to obtain the 2D and 3D structure of resveratrol.Use the TCMSP database to retrieve the molecular and pharmacological characteristics data of resveratrol.2.2 Predict the potential targets of resveratrolRetrieve and combine documents separately on PharmMapper,TCMSP,TCM@TAIWAN,CTD,ETCM and other database platforms,eliminate duplicate data,and obtain a total of potential targets of resveratrol after integration.2.3 Screen targets related to kidney stone diseaseThe key words "nephrolithiasis" and "kidney stone" were searched in genecards,Digene,OMIM and other database platforms respectively,and the literatures were searched.The duplicate data were eliminated and the targets related to kidney stone disease were obtained after integration.2.4 Screen potential targets of resveratrol in prevention and treatment of renal calculiDraw a Venn diagram to obtain the intersection of drug and disease-related targets,which is the potential target of resveratrol in the prevention and treatment of kidney stones.2.5 Construction of the protein-protein interaction network of resveratrol against kidney stonesUsing the STRING 11.0 network platform,input the acquired protein information of the intersection target,set the option in the protein source to humans,and set the custom interaction threshold to 0.9,hide discrete nodes,and generate the protein interaction network diagram.2.6 Topological analysis of protein interaction networkUsing the visualization software Cytospace,with the help of its network analysis function and MCODE plug-in,the key targets and core modules in the interactive network are screened out.2.7 Functional enrichment analysisUse the Metascape platform to perform gene oncology(GO)enrichment analysis and Kyoto gene and genome database(KEGG)pathway enrichment analysis on the potential targets of resveratrol for preventing and treating kidney stones,and visualize the results.2.8 Verification of molecular docking between resveratrol and core targetsWhen performing molecular docking experiments,we first retrieve the protein structure corresponding to the core target from the PDB database,then use the Pymol software to remove the water and ligands of the receptor protein,use the Autodock tools software to modify the receptor protein such as hydrogenation and charge balance,and use AutoDockTools software to hydrogenate and balance the receptor protein.To modify the charge,use the Grid Box command to open the Grid Option tool to process the receptor protein.The size of the ligand binding pocket is determined by the number of lattice points and the spacing between dots in each direction.Therefore,the number of lattice points in each direction,the center of the binding pocket and the spacing of the grid points are adjusted.Autodock Vina software was used to simulate the binding mode of resveratrol with the target protein.The affinity was calculated to measure whether the ligand can effectively bind to the receptor molecule.The lower the energy value is,the better the binding effect is.3.Effect of resveratrol on the adhesion of calcium oxalate stone crystals in vitro3.1 Observation under laser confocal microscopeThe cell model was constructed using 67?g/cm2 calcium oxalate(CaOx)crystals(4mml/L)to continuously stimulate HK-2 cells for 24 hours.Two hours before that,resveratrol(40,80?M)of different concentrations was given.The cells were collected and stained withphalloidin.Cell morphology and crystal adhesion status were observed under the electron microscope.The cells were divided into four groups:blank control group;CaOx treatment group;CaOx+low concentration resveratrol group(40?M);CaOx+high concentration resveratrol group(80?M).3.2 Cell activity testThe cell culture,grouping,and modeling methods are the same as step 1.When the action time was reached,CCK8 reagentwas added,and the absorbance is measured at 450 nm.3.3 Detection of hyaluronic acidThe content of hyaluronic acid(HA)was detected by enzyme-linked immunosorbent assay(ELISA),which was used to evaluate the adhesion of calcium oxalate crystals indirectly.3.4 Detection of LDHThe release of lactatedehydrogenase in groups was detected by the spectrophotometer.4.Resveratrol inhibited renal oxidative stress injury induced by calcium oxalate stonesvia regulating SIRTl/FOXO3a4.1 Effect of resveratrol on oxidative stress indicators(superoxidedismutase,SOD;malondiadehyde,MDA;reactive oxygen species,ROS;catalase,CAT)osteopontin(OPN),kidney injury molecular 1(KIM-1)and SIRT1 expression in renal tubular epithelial cells induced by calcium oxalate crystals(1)The cell model was constructed using 67?g/cm2 calcium oxalate(CaOx)crystals to continuously stimulate HK-2 cells for 24 hours.Two hoursbefore that,resveratrol(40,80?M)of different concentrations was given.When CaOx interacted with HK-2 for 24 hours,cells and culture medium were collected.The cells were divided into four groups:blank control group;CaOx treatment group;CaOx+low concentration resveratrol group(40?M);CaOx+high concentration resveratrol group(80?M).(2)According to the instructions,use kits to measure SOD activity,MDA content and ROS content,SIRT1 deacetylation activity respectively;Western blot to detect SIRT1,FOXO3a,and CAT protein expression levels;co-immunoprecipitation to detect protein expression levels of acetylation FOXO3a.(3)The protein and gene levels of KIM-1 and OPN were determined by Western blot and fluorescence quantitative PCR.4.2 Effect of SIRT1 on oxidative stress indicators in renal tubular epithelial cells induced by calcium oxalate crystals(1)Group and treatment:renal tubular epithelial cells were cultured in vitro and transfected with SIRT1 siRNA and con siRNA respectively.The cells were divided into four groups:CaOx+transfected CON siRNA group;CaOx+transfected CON siRNA+RSV treatment group;CaOx+transfected SIRT1 siRNA;CaOx+transfected SIRT1 siRNA+RSV treatment group.(2)According to the instructions,use kits to measure SOD activity,MDA content and ROS content,SIRT1 deacetylation activity respectively;Western blot to detect SIRT1,FOXO3a,and CAT protein expression levels;co-immunoprecipitation to detect protein levels of acetylation FOXO3a.(3)The protein and gene levels of KIM-1 and OPN were determined by Western blot and fluorescence quantitative PCR.4.3 Effects of resveratrol on metabolic indicators,crystal deposition and renal histopathology of the rat calcium oxalate model(1)Twenty four Wistar rats were randomly divided into three groups to be treated separately:free intake and drinking water;free intake+free drinking water with 1%ethylene glycol;free intake+free drinking water with 1%ethylene glycol+RSV gavage(10mg/kg/d).(2)Retention of Wistar rats:one day before execution,24 hours urine of rats was collected with metabolic cages.5ml blood was taken from the heart.The kidney was dissected,and HE staining and protein immunohistochemical staining were performed.(3)Renal function and urine biochemical test:biochemical analyzer was used to determine blood urea nitrogen(BUN),blood creatinine(Cr),urine(calcium,phosphorus,potassium).Colorimetry method was used to determine the content of oxalic acid in urine.(4)HE stain ing was used to observe the renal crystal deposition and pathological changes.4.4 Effect of resveratrol on SIRT1 expression,KIM-1,OPN and oxidative stress indicators in the kidney of the rat calcium oxalate model(1)The expression of SIRT1,FOXO3a,CAT and acetylated FOXO3a were detected by immunohistochemistry,Western blot and immunocoprecipitation.The activity of SOD,the content of MDA,the activity of ROS and the deacetylation activity of SIRT1 were detected by corresponding kits.(2)The protein and gene levels of OPN and KIM-1 were determined by immunohistochemistry,Western blot and fluorescence quantitative PCR.Results1.First principles study on the absorption of Ca on resveratrol surface1.1 The adsorption energy analysis of Ca adsorption on C14H12O3Firstly,the structural formula of resveratrol was obtained,and the structure of C14H12O3 was optimized to obtain the most stable molecular conformation.According to the molecular structure of resveratrol,five sites were selected as the initial positions for to calculate the adsorption of Ca on C14H12O3.The five original configurations areas follows:(A)Ca is located directly above the center of the 3,5-hydroxybenzene ring;(B)Ca is located directly above the oxygen atom of the 3-hydroxyl group;(C)Ca is located directly above the oxygen atom of the 5-hydroxyl group;(D)Ca is located directly above the oxygen atom of the 4'-hydroxyl group.(E)Ca is located directly above the center of the 4'-hydroxybenzene ring;The calculation results show that in all the initial configurations,the adsorption energies are all negative.Among the five initial sites,the adsorption energy of configuration(a)is the smallest,which is-0.874 eV,and the adsorption distance is 2.39A.1.2 Stable conformation of the adsorption systemBefore and after the adsorption of Ca,the structure of C14H12O3 relaxes.The side view and top view directly show the influence of the adsorption of Ca on the geometric structure of C-4H12O3.1.3 Electronic structure of Ca adsorbed on C14H12O3SurfaceDuring the adsorption,there was charge aggregation between Ca and carbon atoms ofC14H12O3,and at the same time there was a decrease in the number of charges on the other side of Ca facing away from C14H12O3,which indicates that there is an electron transfer from Ca to C14H12O3 during the adsorption process.Further Bader charge analysis showed that during the adsorption process,0.855 e-charge was transferred from Ca to C14H12O3,which is the main feature of Ca adsorption on the surface of C14H12O3.1.4 Comparison of the adsorption energy of Ca on C14H1203 and C2H204As a comparison,the adsorption energy of oxalic acid(C2H2O4)for Ca showed that the adsorption energy of its most stable configuration is-0.68 eV,which was greater than-0.874 eV.2.Network pharmacology study on mechanism of resveratrol against kidneystones2.1 Obtain the chemical structure,molecular and pharmacological properties of resveratrolThe data of 12 main molecules and pharmacological characteristics of resveratrol were obtained,covering the molecular weight,bioavailability and drug-like properties of the drug.2.2 Predict the potential targets of resveratrolRetrieved and combined literature separately on PharmMapper,TCMSP,TCM@TAIWAN,CTD,ETCM and other database platforms to eliminate duplicate data.After integration,a total of 421 potential targets of resveratrol were obtained.2.3 Screen targets related to kidney stone diseaseThe keywords "neprolithias","kidney stone" were retrieved on DisGeNE,OMIM and other database platforms respectively.Combined with the literature,1434 targets related to renal stone diseases were obtained after the data were eliminated and integrated.2.4 Screen potential targets of resveratrol in prevention and treatment of renal calculiThe potential target of resveratrol and the target of renal stone disease were mapped together.115 potential targets of resveratrol were obtained to prevent and treatkidney stones,which were presented in Venn diagram.2.5 Construction of the protein-protein interaction network of resveratrol against kidney stonesThe PPI network includes 115 function nodes,236 function paths,and the average node degree is 5.43.2.6 Topological analysis of protein interaction networkA total of 9 key targets in the RSV anti-kidney stone PPI interaction network were screened out,namely:SIRT1,FOX03a,AKT1,MAPK1,JUN,TP53,VEGFA,SOD1,CAT.Further,using the mcode plug-in of cyberscape,three core modules are selected in the network.2.7 Functional enrichment analysisGO functional enrichment analysis results show that there are a total of 5,025 items enriched in biological processes(BP),involving cellular processes,metabolic processes,biological regulation,stimulus response,biological process regulation,etc.;there are 412 items enriched in cellular components,involving organelles,membrane-enclosed lumen,protein-containing complexes,extracellular regions,synapses,etc.;a total of 575 items are enriched in molecular functions(MF),involving catalytic activity,molecular function regulators,antioxidant activity,molecular transducer activity,transporter activity,etc.These functional pathways are mostly closely related to the processes of oxidative stress,inflammation,metabolism,and damage repair in the body,suggesting that resveratrol may exert its potential to prevent and treat kidney stones by regulating the above-mentioned biological processes.KEGG pathway enrichment analysis results show that there are 233 enriched signal pathways,and the targets are mainly enriched in oxidative stress,apoptosis,inflammation,cell cycle regulation and other aspects.Combined with literature analysis,these targets were closely related to SIRT1/FOXO3a signaling pathway,suggesting that resveratrol may play a role in preventing and treating kidney stones by regulating the oxidative stress response of the kidney mediated by the SIRT1/FOXO3a pathway.2.8 Verification of molecular docking between resveratrol and core targetsThe binding mode between AKT1 and RSV:amino acid residues gly159,gly157,glu191 form hydrogen bond interaction with RSV,asp292,lys179,vai164,lys158,lys163,gly162,phe161,ile186,his194,thr195 form hydrophobic interaction with RSV,and the affinity is-7.9 kcal/mol.The binding mode between cat and RSV:amino acid residues ala133,arg112,arg365,thr361 form hydrogen bond interaction with RSV,his362,arg72,ser114,phe132,gly131,gly147,val146,his75,tyr358,va173 form hydrophobic interaction with RSV,and the affinity is-9.0 kcal/mol.The binding mode between FOXO3a and RSV:amino acid residues gly198,leu 180,ser200 form hydrogen bond interaction with RSV;ser181,tyr184,asp199,ala204,lys207 form hydrophobic interaction with RSV;the affinity is-5.6 kcal/mol.The binding mode between JUN and RSV:the amino acid residue Asn17 forms a hydrogen bond interaction with RSV,and Tyr18,Ala15,Lys14 forms a hydrophobic interaction with RSV,and the affinity is-4.9 kcal/mol.The binding mode between MAPK1 and RSV:amino acid residues met108,asp167,asn154,lys54 form hydrogen bond interaction with RSV,cys166,leu156,leu107,asp106,Ala52,gln105,va139 form hydrophobic interaction with RSV,and the affinity is-7.2 kcal/mol.The binding mode of SIRT1 and RSV:the amino acid residues lys304 and RSV form hydrogen bond interaction,glu300,glu214,asp298,pro212,ala295,tyr301,asp289,pro291,asp292 form hydrophobic interaction with RSV,and the affinity is-7.5 kcal/mol.The binding mode between SOD1 and RSV was hydrogen bond interaction between lys23 and RSV,hydrophobic interaction between gly33,va129,trp32 and RSV,and the affinity energy was-5.2 kcal/mol.The binding mode between TP53 and RSV:the amino acid residues leu330 and leu348 form hydrogen bond interaction with RSV,and asn345,phe338,phe341,arg342 and Arg344 form hydrophobic interaction with RSV,with an affinity of-6.1 kcal/mol.The binding mode of VEGFA and RSV:amino acid residues tyr45,ile43,glu44,glu42,phe36,pro40 formed hydrophobic interaction with RSV,and the affinity was-5.4 kcal/mol.3.Effect of resveratrol on the adhesion of calcium oxalate stone crystals in vitro3.1 Observation under laser confocal microscopeObserved under a microscope,resveratrol can repair cell morphology and reduce the adhesion of calcium oxalate stone crystals.3.2 Cell viability testResveratrol could reduce the toxic effect of CaOx crystal on HK-2 cells,and the cell viability increased significantly(P<0.05),indicating that resveratrol had the effect of inhibiting cell apoptosis or necrosis.3.3 Changes in HA contentCompared with the blank group,the HA concentration of the oxidative injury group was significantly higher,while the HA concentration of the resveratrol group was significantly lower than that of the control group.3.4 Detection of lactate dehydrogenase(LDH)The blank control group had the lowest LDH content.After adding CaOx crystals,the LDH content increased significantly(P<0.05).After the intervention of resveratrol,the LDH content decreased significantly(P<0.05),suggesting that resveratrol has a significant cell repair function.4.Resveratrol inhibited calcium oxalate-induced oxidative stress injury of renal tubular epithelial cells via upregulating SIRTl/FOXO3a,thereby inhibiting the formation of kidney stones4.1 Resveratrol ameliorated calcium oxalate-induced oxidative stress injury of renal tubular epithelial cells and increased the expression of SIRT14.1.1 Changes of SOD,CAT,ROS and MDA in HK-2 cellsAfter calcium oxalate crystals intervention,SOD and CAT in HK-2 cells decreased significantly(P<0.05),while ROS and MDA increased significantly(P<0.05).After resveratrol intervention,SOD activity and CAT expression increased significantly(P<0.05),while ROS and MDAdecreased significantly(P<0.05).4.1.2 Changes of OPN and KIM-1 in HK-2 cellsAfter calcium oxalate crystals intervention,the expression of OPN and KIM-1 in HK-2 cells increased significantly(P<0.05).After resveratrol intervention,the expression levels of OPN and KIM-1 decreased significantly(P<0.05).4.1.3 Changes of SIRT1,SIRT1 deacetylation activity,FOXO3a and acetylated FOXO3a in HK-2 cellsResveratrol significantly reversed the decrease of SIRT1 protein expression induced by calcium oxalate crystal,and increased SIRT1 deacetylation activity and FOXO3a expression(P<0.05).At the same time,the expression of acetylated FOXO3a in the resveratrol group cells was significantly lower than that in the calcium oxalate group(P<0.05).4.2 SIRT1 was involved in the regulation of oxidative stress in renal tubular epithelial cells induced by calcium oxalate crystals4.2.1 Changes in oxidative stress indicators such as SOD,CAT,ROS,and MDA and changes in FOXO3a and acetylated FOXO3a in HK-2 cells after SIRT1 RNA interferenceCompared with CON siRNA transfected group,SIRT1 siRNA transfected renal tubular epithelial cells significantly reduced the gene and protein expression of SIRT1,decreased the activity of SOD,the content of CAT and the expression of FOXO3a,and increased the total amount of ROS,the content of MDA and the expression of acetylated FOXO3a(P<0.05).After resveratrol treatment,the oxidative stress indicators in the CON siRNA transfected cells improved significantly,the FOXO3a protein expression level increased and the acetylated FOXO3a expression decreased(P<0.05).In contrast,the improvement of oxidative stress indicators in SIRT1 siRNA transfected cells was not obvious,the expression of FOXO3a protein slightly increased and the expression of acetylated FOXO3a slightly decreased(P<0.05).4.2.2 Changes of OPN and KIM-1 in HK-2 cells after SIRT1 RNA interferenceCompared with the CON siRNA transfection group,the expression levels of OPN and KIM-1 in SIRT1 siRNA transfection group increased(P<0.05).After the resveratrol intervention,the expression levels of OPN and KIM-1 in both groups decreased in varying degrees,but the expression level of SIRT1 siRNA transfection group was still high(P<0.05).4.3 Resveratrol improved renal metabolism,crystal deposition and renal histopathology in the rats calcium oxalate modelResveratrol can reduce blood urea nitrogen and creatinine,and reduce the contents of oxalic acid,calcium and phosphorus in urine(P<0.05).Resveratrol could reduce the crystal deposition in the kidney of calcium oxalate rats,improve its pathological abnormalities,and inhibit the formation of stones and protect kidneys.4.4 Resveratrol improved the oxidative stress injury of the kidney in the rats calcium oxalate model and increased the expression of SIRT14.4.1 Changes ofSOD,CAT and MDA in rats kidneyCompared with the normal control group,the activity of SOD and the expression of CAT in the kidney of the model rats were significantly decreased,while the content of MDA was significantly increased(P<0.05).After resveratrol treatment,the above oxidative stress indicators showed significant improvement(P<0.05).4.4.2 Changes of OPN and KIM-1 in rats kidneyConsistent with cell experiments,the expression of OPN was the least in the normal control group and significantly increased in the model rats(P<0.05).After resveratrol intervention,the expression of OPN decreased significantly compared with the model rats,and was directly proportional to the treatment dose.The expression level of KIM-1 was similar to OPN(P<0.05).4.4.3 Changes of SERT1 and SIRT1 deacetylation activity,FOXO3a,acetylated FOXO3a in rats kidneyCompared with normal rats,expressions of SIRT1 and FOXO3a in the kidney were significantly reduced,and SIRT1 deacetylation activity was decreased,while expression of acetylated FOXO3a was significantly increased(P<0.05).After resveratrol treatment,above-mentioned indicators were reversed.Conclusion1.The atom Ca can be stably adsorbed on the surface of the molecule C14H12O3 and competitively inhibit the formation of calcium oxalate.This is the first time to elaborate the mechanism of prevention and treatment of calcium oxalate kidney stones by C14H12O3 from the perspective of atoms and molecules,which provides ideas and basis for the research and development of resveratrol-based drugs.2.The results of network pharmacological analysis suggest that resveratrol can prevent and treat kidney stones through multiple targets and pathways.The oxidative stress response of the kidney mediated by the SIRT1/FOXO3a pathway may play an important role in the process of resveratrol against kidney stones,which provides an important reference for further in vitro and in vivo experiments.3.In vitro,resveratrol can inhibit the adhesion of calcium oxalate crystal to renal tubular epithelial cells,increase cell viability,reduce the secretion of hyaluronic acid and lactate dehydrogenase,and has the potential of inhibiting cell apoptosis and repairing damaged cells.4.Resveratrol had a pharmacological effect of inhibiting the formation of stones.The mechanism might to be related to ameliorate calcium oxalate crystals-induced renal oxidative stress injury via SIRT1/FOXO3a pathway. |
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