Research On The Treatment And Treatment Of Diabetic Kidney Disease Based On The Mechanism Of The Kidney Collaterals And Wind Theory And Its Mechanism Of Action

Study one:Study on“treating Diabetic Kidney Disease from the wind” based on data mining technologyObjectivesResearch professor Zhao Jinxi’s medical case for treating Diabetic Kidney Disease(DKD),thus revealing the clinical application rules of "treating DKD from the wind".MethodsCollect professor Zhao Jinxi’s medical cases for treating DKD in the clinic and treatment area,and analyze the syndromes,symptoms,tongue,pulse,prescription drugs by EXCEL,SPSS,WEKA,UCINET.Frequency analysis,cluster analysis,association rule analysis,and social network analysis are carried out for researching prescription drugs,so as to reveal the clinical application rules of "treating DKD from the wind".ResultsThe results of social network analysis of prescription drugs show that the core prescription of stage Ⅲ DKD is composed of drugs such as nourishing qi and blood,activating blood circulation and removing stasis,dispel wind and dredge collaterals,clearing dampness and heat,clearing heat and reducing fire,including Huang qi,Dang gui,Ge gen,Dan shen,Chuan xiong,Gui jian yu,Niu bang zi,Chuan shan long,Can sha,Tu fu ling,Bi xie,Shi wei,Huang qin.The core prescription of stage Ⅳ DKD is composed of drugs such as nourishing qi and blood,activating blood circulation and removing stasis,dispel wind and dredge collaterals,clearing dampness and heat,clearing heat and reducing fire,including Huang qi,Dang gui,Chuan xiong,Dan shen,Gui jian yu,Niu bang zi,Chuan shan long,Can sha,Tu fu ling,Bi xie,Shi wei,Zhu ling,Fu ling,Huang qin.The core prescription of stage V DKD is composed of drugs such as nourishing qi and blood,activating blood circulation and removing stasis,ascending lucidity and descending turbidit,dredging the internal organs and releasing the turbid,strengthening the spleen and regulating the stomach,clearing dampness and heat,clearing damp and promoting diuresis,dispel wind and dredge collaterals,including Huang qi,Dang gui,Chuan xiong,Dan shen,Chan tui,Jiang can,Jiang huang,Da huang,Xiang fu,Su ye,Chen pi,Ban xia,Tu fu ling,Bi xie,Shi wei,Zhu ling,Fu ling,Gui jian yu,Niu bang zi,Chuan shan long,Can sha.The results of cluster analysis and association rule analysis mainly showed that the commonly used drug pairs and drug combinations.Huang qi,Dang gui,Chuan xiong,Dan shen nourishing qi and blood,activating blood circulation and removing stasis.Chen pi,Ban xia,Cang zhu,Chao bai zhu strengthening the spleen and regulating the stomach,clearing damp.Xu duan,Sang ji sheng tonifying kidney and strengthening waist.Sang ye,Ju hua,Xia ku cao dispel wind,clearing liver and improving vision.Bi xie,Shi wei,Tu fu ling,Jin qian cao,Huzhang,She cao,Ban zhi lian clearing dampness and heat.Fu ling,Zhu ling clearing damp and promoting diuresis.Chan tui,Jiang can,Jiang huang,Da huang ascending lucidity and descending turbidit,Relieving turbidity and detoxification.Huang lian,Rou gui Communicating heart and kidney.ConclusionIn the treatment of DKD,professor Zhao Jinxi paid attention to the treatment methods of nourishing qi and blood,activating blood circulation and removing stasis,dispel wind and dredge collaterals,clearing dampness and heat.According to the pathogenesis of kidney collateral wind movement,professor Zhao Jinxi applied the drug combination of Gui jian yu,Niu bang zi,Chuan shan long,Can sha.According to the internal movement of liver wind,applied the drug combination of Sheng long gu,Sheng mu li.According to the wind movement of body collateral,applied the drug combination of Ji xue teng,Qing fengteng,Di long,Shui zhi.According to the wind movement of eye collateral,appliedthe drug combination of Sang ye,Ju hua,Xia ku cao.In addition to the above commonly used wind medicine,there are also various wind medicine in other commonly used drug pairs and drug combinations,which reflects the academic characteristics of professor Zhao Jinxi in treating DKD.Study two:Study on the mechanism of the treatment of DKD with the method of nourishing qi,dispelling wind and dredging collaterals based on network pharmacologyObjectivesScreen the active components and targets of Yi qi qu feng tong luo prescription(Huang qi,Gui jian yu,Niu bang zi,Chuan shan long,Can sha)by the method of network pharmacology analysis,and predict the treatment mechanismMethodsSearch "Huang qi","Gui jian yu","Niu bang zi","Chuan shan long","Can sha" on the official website of TCMSP database,and the data of drug active ingredients were supplemented by consulting the relevant literature.Import the above files into the Swiss Target Prediction database to obtain the potential target information of the active ingredients of this prescription.Search the key word of "diabetic nephropathy" in the disease gene association database to obtain the gene and target protein information related to DKD.Draw the venny map of the common target of prescription drugs and diseases through the venny2.1 online software.The data of active ingredients,common target of Yi qi qu feng tong luo prescription and diabetic kidney disease were input into the software of Cytoscape,and the interaction network diagram of "Yi qi qu feng tong luo prescription-active ingredient target-diabetic kidney disease target"was drawn.Import the common target data of prescription and disease into STRING database for search,PPI networkmap was constructed and sorted according to the correlation between proteins.Analyse the key target gene function of the common target of Yi qi qu feng tong luo prescription and DKD through GO and KEGG.ResultsAccording to the network analysis results of rescription-active ingredient target-disease target,Kaempferol can reduce blood glucose and inhibit the production of glycosylation end products.Isorhamnetin has anti-inflammatory and hypoglycemic effects.Among the drug disease common targets,the decrease of SHBG level is related to the occurrence of type 2 diabetes.The PPI network map show that MAPK1,also known as extracellular signal regulated kinase 2(ERK2),is the key kinase of ERKs signaling pathway.MAPK14 is the P38a belong to p38MAPK protein family,an important protein in P38-MAPK signaling pathway.AKT1 is an important member of AKT family,an important kinase of PI3K/AKT signaling path way.S TAT1,STAT3 and JAK2 are important proteins of JAK/STAT signaling pathway.TNF and IL2 are important cytokines involved in the immune and inflammatory response of the body.ICAM-1 is an intercellular adhesion molecule,which can promote the adhesion of inflammatory cells in the inflammatory response area.The results of GO analysis indicate that the mechanism of Yi qi qu feng tong luo prescription in the treatment of DKD may be closely related to PI3K/AKT signaling pathway and MAPK signal pathway.The results of KEGG analysis showed that the common target was mainly concentrated in diabetes,tumor,infection and other diseases,among which AGE-RAGE signaling pathway,PI3K/AKT signaling path way,VEGF signaling pathway,MAPK signaling pathway were found to be closely related to the occurrence and development of diabetes in recent years.ConclusionThe mechanism of Yi qi qu feng tong luo prescription in the treatment of DKD may be closely related to the inhibition of inflammatory response,and involves a variety of inflammatory related signal transduction pathways,including PI3K/AKT signaling pathway,P38-MAPK signaling pathway,ERKs signaling pathway,AGE-RAGE signaling pathway,VEGF signaling pathway,JAK/STAT signaling pathway.Study three:Study on the mechanism of the DKD treatment with the method of nourishing qi,dispelling wind and dredging collateralsObjectivesReveal the internal mechanism of Yi qi qu feng tong luo prescription in the treatment of DKD by cell experiment.MethodsThirty male Wistar rats of SPF grade were fed with normal diet for one week.The rats were randomly divided into six groups:blank group,Yi qi qu feng tong luo group,Qu feng tong luo group,blocker blank group,blocker Yi qi qu feng tong luo group,blocker Qu feng tong luo group,five rats in each group.Eight hours before the last gastric perfusion,the rats were fasted and couldn’t help drinking water,and aseptic blood collection was carried out in the femoral artery of rats.The mesangial cells were divided into six groups.The first group:cell+fetal bovine serum+low sugar DEMEM culture medium.The second group:cell+blank rat serum+low sugar DEMEM culture medium.The third group:cell+ blank rat serum+high sugar DEMEM culture medium.The fourth group:cell+blank ratserum+blocker+high sugar DEMEM culture medium.The fifth group:cell+whole prescription containing serum+high sugar DEMEM culture medium.The sixth group:cell+disassembled prescription containing serum+high glucose demem culture medium.We stern blot was used to detect the expression of P38-MAPK,ICAM-1,MCP-1 and PCR was used to detect the gene expression of P38-MAPK,ICAM-1,MCP-1,IL-6,IL-1β,TGF-β1,TNF-α.ResultsThe results of P38-MAPK PCR showed that there was significant difference between group two and group three,indicating that P38-MAPK signal pathway of mesangial cells was over activated in high glucose environment.Group three and group five,group three and group six,group five and group six all showed significant differences,indicating that whole prescription and disassembled prescription could inhibit P38-MAPK signal pathway,while the inhibition of whole prescription was stronger than that of disassembled prescription.The Western blot results of P38-MAPK showed that there was significant difference between the two groups,indicating that high glucose environment could lead to the increase of P38-MAPK protein expression.The Western blot results of MCP-1 showed that there were significant differences between group three and group five,group three and group six,group five and group six,which indicated that the whole prescription and disassembled prescription can inhibit the expression of MCP-1 protein,and the inhibition of the whole prescription was stronger than that of disassembled prescription.The PCR results of MCP-1 in this study showed that there were significant differences between group three and group five,and group three and group six,indicating that the whole prescription and the disassembled prescription can inhibit the expression of MCP-1 gene.Western blot analysis of ICAM-1 showed that there were significant differences between group 1 and group three,group two and group three,indicating that high glucose environment can stimulate the over expression of ICAM-1 protein.The PCR results of ICAM-1 showed that there were significant differences between group three and group five,group three and group six,which indicated that the whole prescription and disassembled prescription can inhibit the overexpression of ICAM-1 gene.The results of PCR detection of IL-1β,IL-6 and TNF-α showed that there were significant differences between group two and group three,group three and group five,group three and group six,which indicated that the high glucose environment could stimulate the mesangial cells to oversecrete IL-1β,IL-6,TNF-α and other inflammatory factors,while the whole prescription and disassembled prescription can inhibit the oversecretion of IL-1β,IL-6,TNF-α and other inflammatory factors.The PCR results of TGF-β1 showed that there were significant differences between group three and group five,group three and group six,which indicated that the whole prescription and disassembled prescription can inhibit the oversecretion of TGF-β1.ConclusionHigh glucose environment can activate P38-MAPK signaling pathway,resulting in the increase of inflammatory cytokines such as ICAM-1,MCP-1,IL-1β,IL-6,TNF-α,TGF-β1.The whole prescription has the stronger inhibition effect on P38-MAPK signaling pathway than the disassembled prescription.It shows that treating DKD from the wind can inhibit P38-MAPK signal pathway and reduce the excessive secretion of various inflammatory related cytokines.Combining the treatment strategy of nourishing qi,activating blood circulation and removing stasis,dispel wind and dredge collaterals can get better efficacy than the strategy of dispel wind and dredge collaterals.