Protective Effect And Its Mechanism Of Yishenhuoxuefang On Early Diabetic Nephropathy In Rats

Objective: To observe the protective effect and its mechanism of Yishenhuoxuefang(YSHXF) on early diabetic nephropathy in rats.Methods:90Wistar rats, male,10rats were taken as control group, before the rest therats were fasted12h, model group rats were intraperitoneal injected STZ50mg/kg; under thesame conditions, control group were injected dose sterile citrate buffer. Take successfulmodel rats, they were randomly divided into five groups: model group, YSHXF0.5,1.0,2.0g/kg group, positive drug (Benazepril) group. All the animals were gavage (ig)administration for8weeks in accordance with the above scheme daily. Body weights wererecorded weekly, biweekly tail vein blood, fasting blood glucose with a glucose meter. Oneday before the end of the experiment rats were fasted water collected24h urine. Fastingblood glucose, after ig administration1h, intraperitoneal injection of10%chloral hydrate30mg/kg anesthesia, abdominal aortic blood, centrifugal separation of serum, measured theindicators, collected rats kidney, pancreas, and observed morphological.Results:①Model group rats by intraperitoneal injection of STZ50mg/kg, after thatperformance: reduced activity; polydipsia, the average water consumption is two to threetimes than control group; polyuria, obviously wet litter daily need of replacement1-2times;weight decreased; listlessness, color gray, rough. Compared with model group, YSHXF2.0g/kg group can significantly improve water intake in rats, an increase in urine output,weight loss, malaise mental state and other symptoms;②Compared with control group,blood glucose of model group rats were significantly higher in0,2,4,6,8weeks (P<0.01);Compared with model group, YSHXF0.5,1.0,2.0g/kg group can significantly lower bloodglucose levels in rats after treatment the drug two weeks (P<0.05or P<0.01), and continueduntil8weeks;③Compared with control group, serum INS content of model group ratswere significantly lower, and CHO and TG levels significantly increased (P<0.01);Compared with model group, YSHXF1.0,2.0g/kg group could significantly increase serumINS content, reduce CHO and TG levels (P<0.05or P<0.01);④Compared with control group, urine Crea, mALB, ALB, β2-MG content of model group were significantly increased(P<0.01); Compared with model group, YSHXF2.0g/kg group can significantly reduceurine Crea, mALB, ALB, β2-MG content (P<0.05or P<0.01);⑤Compared with controlgroup, the serum UREA, BUN content and kidney weight/body weight of model group weresignificantly higher (P<0.01); Compared with model group, YSHXF2.0g/kg couldsignificantly reduce UREA, BUN content and kidney weight/body weight (P<0.05orP<0.01);⑥Compared with control group, the serum T-SOD, GSH-PX, CAT activity andT-AOC of model group were decreased, H2O2, MDA content and NOS activity wassignificantly increased (P<0.05or P<0.01); Compared with model group, YSHXF1.0,2.0g/kg group could increase serum T-SOD, GSH-PX, CAT activity and T-AOC,reducing H2O2, MDA content and NOS activity (P<0.05or P<0.01);⑦Compared withcontrol group, plasma TXB2content of model group was significantly increased, and6-kelo-PGF1α content decreased (P<0.01); Compared with model group, YSHXF0.5,1.0,2.0g/kg group could decreased plasma TXB2content, increased6-kelo-PGF1αcontent (P<0.05or P<0.01);⑧Compared with control group, the renal tissue of modelgroup rats were seen significant pathological damage; Compared with model group, YSHXF0.5g/kg dose group, no significant difference in pathological changes, but YSHXF1.0,2.0g/kg dose group reduce renal pathology damage;⑨Compared with control group,model rats TGF-β and Smad2/3gray values decreased, indicating that TGF-β and Smad2/3expression was increased (P<0.01); Compared with the model group, YSHXF1.0,2.0g/kgand Benazepril group TGF-β and Smad2/3gray values increased, indicating TGF-β andSmad2/3expression reduced (P<0.01).Conclusion: YSHXF can significantly improve the symptoms of diabetes in EDN rats,regulate blood lipid metabolism, and protect kidney function and structural damage, possiblythrough its mechanism against oxidative damage of free radicals, correcting the imbalance ofvascular endothelial growth factor, inhibiting TGF-β signal pathway.