Meta Analysis Of Fermented Cordyceps Sinensis Powder In The Treatment Of DKDⅢ And Ⅳ And Its Mechanism On DKD Rats

Objective: Meta-analysis of the clinical efficacy of fermented Cordyceps sinensis powder preparation Jinshuibao in treating stage Ⅲ and Ⅳ of diabetic kidney disease.DKD rat model was established by feeding high-sugar and high-fat feed combined with intraperitoneal injection of streptozotocin.Compare the effects of different process fermented Cordyceps sinensis powder on DKD rats,select the process with the best effect,and further study the mechanism of action of fermented Cordyceps sinensis powder on DKD rats.Methods:1.Computer search The Cochrane Library,Pub Med,Web of Science,CNKI,VIP,Wan Fang Data,and collected clinical randomized controlled trials of Jinshuibao in the treatment of diabetic kidney disease.The search time was from the establishment of the database to March 1,2019.Meta-analysis was performed using Rev Man 5.2software after screening the literature,extracting the data,and evaluating the quality according to the cochrane systematic review method.2.DKD rat model was established by feeding high sugar and high fat diet combined with intraperitoneal injection of streptozotocin.Six different processes of fermented Cordyceps sinensis powder were given at high and low doses.FPG levels in DKD rats were measured using a blood glucose meter.Kit method serum BUN,Scr,SOD,MDA,ALT,AST,hs-CPR,urine Ucr,ALB,and urine protein levels were detected in DKD rats.HE staining was used to detect pathological changes in DKD rats.3.DKD rat model was established by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin,and the screened fermented Cordycepssinensis powder B was given low,medium,and high doses,and kits were used to detect serum BUN,Scr,TC,TG,LDL-C,HDL-C,SOD,MDA,ALT,AST,IL-6,IL-8,TNF-α,hs-CRP,GSP,MPC-1,TGF-β1,urine Ucr,ALB,and urine protein content in DKD rat.HE staining were used to detect pathological morphological changes in DKD rats.4.DKD rat model was established by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin.The selected fermented Cordyceps sinensis powder B was given to extract kidney tissue protein.Protein samples were analyzed by Nano-LC-LTQ-Orbitrap.Using protein discovery software for protein identification,SIEVE software for quantitative and qualitative analysis,and Uniprot database(https://www.uniprot.org/)for protein-related information.Results:1.A total of 11 RCTs were included,including 782 patients.Meta analysis results show that Jinshuibao can improve the renal function of patients,reduce urea nitrogen[SMD =-1.15,95% CI(-1.94,-0.36),P = 0.004] and serum creatinine [SMD =-0.64,95% CI(-1.12,-0.02),P = 0.04],improved triglyceride [SMD =-2.26,95% CI(-3.54,-0.98),P = 0.0005] and total cholesterol [SMD =-1.16,95% CI(-2.03,-0.28),P =0.009] level,decreased urine microalbumin [SMD =-2.53,95% CI(-4.43,-0.64),P =0.009] level.Subgroup analysis showed that Jinshuibao effect on stage Ⅳ patients[SMD =-1.63,95% CI(-2.99,-0.28),P = 0.02] was better than that on stage Ⅲpatients in reducing urea nitrogen levels [SMD =-0.86,95% CI(-1.89,0.16),P =0.10].Effect of Jinshuibao on patients with stage Ⅳ in improving serum creatinine level [SMD =-1.21,95% CI(-2.06,-0.36),P = 0.005] is better than the effect on patients with stage Ⅲ [SMD =-0.35,95% CI(-1.12,0.43),P = 0.38].2.In the DKD model group,FPG and renal weight levels were significantly increased(P<0.01),body weight was significantly decreased(P<0.01),serum BUN,ALT,hs-CRP levels were significantly increased(P<0.01),and urine Ucr levels were down-regulated(P<0.01),and ALB and urine protein levels were significantly increased(P<0.01).In the low-dose group of fermented Cordyceps sinensis powder,all six kinds of powders could reduce the increase of body weight,Ucr,Ccr levels(P<0.01,P<0.05),and lower the levels of FPG,BUN,Scr,and urine protein(P<0.01,P<0.05).CS A,CS B,CS F can reduce kidney weight level(P<0.01,P<0.05).CS A,CS B,CS D,CS E,CS F can reduce kidney weight/weight level(P<0.01,P<0.05).CS A,CS B,CS C,CS D,and CS F can reduce ALT levels(P<0.01,P<0.05),and CS A,CS B,CS C,and CS E can increase SOD levels(P<0.01,P<0.05).CS C,CS E,CS F can reduce ALB level(P<0.01,P<0.05),CS F can reduce hs-CRP level(P<0.05).In the high-dose group of fermented Cordyceps sinensis powder,all of the six powders could reduce hs-CRP levels(P<0.01,P <0.05),and CS A,CS B,and CS F could reduce kidney weight levels(P<0.01,P<0.05).CS B can reduce FPG,kidney weight /weight level(P<0.01).CS B,CS C,CS D,CS F can reduce BUN levels(P<0.01,P<0.05).CS A,CS D can decrease the level of Scr(P<0.01,P<0.05).CS D can increase Ucr level(P<0.05).CS A,CS B,CS C,CS D,CS F can reduce urine protein levels(P<0.01,P<0.05).CS A and CS F can reduce ALT levels(P<0.01,P<0.05),and CS B,CS C,and CS D can reduce MDA levels(P<0.01,P<0.05).In the kidney tissue structure.In the DKD model group,some glomerular hypertrophy,enlarged renal capsules,and vacuolar degeneration of renal tubular epithelial cells,some tubular lumens expanded,accompanied by exfoliation of epithelial cells,increased renal interstitial components,and partial inflammation was seen sex cell infiltration.The fermented Cordyceps sinensis powder group can improve the above-mentioned situation to different extents,indicating that the fermented Cordyceps sinensis powder can improve the related indexes of kidney function,protect the kidney tissue structure from being destroyed and thus achieve the purpose of protecting the kidney.3.In the DKD model group,the levels of FPG and kidney weight were significantly increased(P<0.01)and body weight was significantly reduced(P<0.01).Serum BUN,Scr,TC,TG,LDL-C,ALT,AST,IL-6,IL-8,TNF-α,hs-CRP,GSP,MCP-1,TGF-β1significantly increased(P<0.01,P<0.05).SOD levels decreased(P<0.05).Ucr,ALB level decreased(P<0.01).And the urine protein level increased significantly(P<0.01).Compared with the model group,each dose group of fermented Cordyceps sinensis powder B can reduce kidney weight,kidney weight/body weight,FPG,BUN,Scr,urine protein,ALB,TC,LDL-C,MDA,IL-6,IL-8,TNF-α,hs-CRP,FFA,GSP,MCP-1,TGF-β1 to varying degrees.Increase weight,Ucr,Ccr,HDL-C,SOD levels(P<0.05,P<0.01),and the effect of fermented Cordyceps sinensis powder B high-dose group is more obvious,and it can improve the morphological damage of kidney tissue to varying degrees.4.The results of proteomics analysis showed that compared with the model group,the differential protein of fermented Cordyceps sinensis powder group was mainly related to related proteins such as sugar metabolism,energy metabolism,substance transport and immune inflammation.Conclusion:1.Fermented Cordyceps sinensis powder preparation Jinshuibao can improve some renal function indexes in patients with diabetic kidney disease Ⅲ and Ⅳ,and is more suitable for improving indexes of urea nitrogen and blood creatinine in stage Ⅳpatients and reducing total cholesterol and triglyceride levels in stage Ⅲ patients.Due to the limited number and quality of included studies,they still need to be validated in clinical studies.2.Six different processes of fermented Cordyceps sinensis powder have obvious renal protection effect on DKD rats,and can improve the renal function index and the microstructure of kidney tissue to different degrees.Fermenting Cordyceps sinensis powder B has a better effect.3.Fermented Cordyceps sinensis powder B has a certain kidney protective effect on DKD rats,which is related to its ability to reduce blood glucose,regulate blood lipids,improve oxidative stress and inflammation levels,and inhibit renal fibrosis.4.Proteins such as TKT,FBPase,IDHs,14-3-3ε,α-2u globulin,MUPs,and myosinⅦ are potential targets for fermented Cordyceps sinensis powder to control DKD.