| Objective:Diabetic nephropathy (DN) develops in approximately30-40%ofdiabetic patients, representing the leading cause of end-stage renal diseaseworldwide. a large body of evidence indicates that oxidative stress is thecommon denominator link for the major pathways involved in thedevelopment and progression of diabetes and DN. Hyperglycemia inducesoxidative stress either by the direct generation of reactive oxygen species(ROS) or by altering the redox balance. Superoxide dismutase (SOD) is one ofthe important enzymes in the antioxidant system, it could convert O2tohydrogen peroxide (H2O2), which is further transformed into H2O and O2.Thereby SOD is regarded as an important marker to assess the function ofantioxidant system. ROS could cause the peroxidation of lipid, protein, thuscausing cell and tissue damage. Methane dicarboxylic aldehyde (MDA) is aproduct formed as an end product of lipid peroxidation of cellularpolyunsaturated fatty acids. Measurement of MDA helps to assess the degreeof tissue damage. It has been documented that hyperfiltration was the initialfactor of diabetic nephropathy. Increased production of nitric oxide (NO) hasbeen speculated to be responsible in the pathogenesis of hyperfiltration.Danhong injection (DHI), a traditional Chinese medicine, the formula isapplied extensively to cardiovascular and cerebrovascular disease viasynergistic anti-inflammatory, antioxidative and antiapoptotic effects. Recently,DHI has been extensively applied to treat diabetes and its complicationssynergisticly, which has been achieved good effect. However, the exactmechanisms remain unclear. Metformin, which can play a role in diabetesthrough a variety of mechanisms, including improving regulating glucose and insulin resistance, is extensively applied to diabetes. Recent studies haveshown its renal protective effect. In this study, type1diabetic rat model wasestablished by intraperitoneal injection of streptozotocin (STZ). DHI andmetformin were applied to the diabetic rats. The activity of SOD, content ofMDA and NO in the rat kidney were detected by the use of pathologicalmorphology and colorimetry to explore the possible effect of oxidative stressand glomerulihyperfiltration in the occurrence and development of DN. At thesame time, the renal protective mechanism of DHI and metformin wereinvestigated in this study.Methods:48male SD rats were divided into two groups randomly:10normalcontrol rats (group A) and38test rats. The test rats were injected with STZ(55mg/kg) intraperitoneally.72hours later, the rats whose blood glucose (BG)levels were higher than16.7mmol/L in the subsequent3days were consideredas type1diabetic rats. The diabetic rats were randomly divided into threegroups: diabetic control rats (group B), diabetic rats treated with2ml/kg.dDanhong injection (group C) and diabetic rats treated with300mg/kg.dmetformin (group D). The experiment lasted8weeks. BG and body weightwere measured at the beginning of the experiment and the end of8weeks. Atthe end of8weeks,24-hour urine was collected and24-hour urinary albuminwas measured by radioimmunoassay. At the end of8weeks, serum creatinine(Scr), blood urea nitrogen (BUN), serum triglyceride (TG), total cholesterol(TC), low density lipoprotein (LDL) were detected. Kidney specimens wereprepared for H.E stain to observe the changes of renal pathomorphology. Theactivity of SOD, content of MDA and NO in the kidney homogenate wereassayed by ultraviolet spectrophotometer respectively. All the experimentaldata dealt with SPSS16.0. If multiple sets of variables were consistent withhomogeneity of variance, analysis of variance (ANOVA) was used to comparemulti-group variables. If multiple sets of variables were not consistent withhomogeneity of variance, Nonparametric tests was used. Results:1The body weight and BG of rats in every group at the end of8weeks:the body weight of group B, C and D were significantly lighter than group A(all P<0.01). There was no significant difference in weight of group B, C andD (all P>0.05). The BG of group B, C and D were significantly higher thangroup A (all P<0.01). There was no significant difference in BG of group Band C(P>0.05). However, the BG of group D was significantly lower thangroup B(P<0.01).2The biochemical parameters of rats in every group at the end of8weeks: Serum TC, TG, LDL of group B, C, and D were significantly higherthan group A (all P<0.01), while serum TC, TG, LDL of group C and Ddecreased obviously compared with group B (all P<0.01).Serum BUN, Scr ofgroup B, C and D were significantly higher than group A (all P<0.01), whileall the above parameters decreased obviously in group C compared with groupB (P<0.05, P<0.01). Serum BUN, Scr decreased obviously in group Dcompared with group B (all P<0.01).3The24h urinary albumin, urine volumes of24h and renal hypertrophyindex of rats in every group at the end of8weeks: the24h urinary albumin,urine volumes of24h and renal hypertrophy index of group B, C and D wassignificantly higher than group A (all P<0.01), while all the above parametersdecreased obviously in group C compared with group B (P<0.01, P<0.01,P<0.05),24h urinary albumin and renal hypertrophy index decreasedobviously in group D compared with group B (all P<0.01). There was nosignificant difference in urine volumes of24h of group B and D(P>0.05).4The oxidative stress parameters of rats in every group at the end of8weeks: SOD of group B was significantly lower than group A (P<0.01), therewas no significant difference in SOD of group A,C and D(all P>0.05). Whilethe parameter increased obviously in group C and D compared with group B(all P<0.01). MDA increased obviously in group C and D compared withgroup B (all P<0.01). There was no significant difference in MDA of group Aand C(P>0.05). MDA of group C and D were significantly lower than group B(all P<0.01). NO of group B, C and D were significantly higher than group A (all P<0.01),while NO of group C and D decreased obviously compared withgroup B (all P<0.01).5H.E stain shows, in group B, the average sectional area of glomerulusbecame larger and there were significant mesangial matrix hyperplasia. Sometubular lumens were narrowed. There were vacuolar degeneration in renaltubular cells. The glomerular lesions of group C and D were significantlylighter than group B.Conclusion:1The activity of SOD decreased significantly in the kidney of diabeticrats, while the content of MDA and NO in diabetic rats were significantlyhigher than the nomal control group, which shown that the oxidative stress andglomerulihyperfiltration were involved in the development and progression ofDN.2DHI and metformin could increase the activity of SOD and decreasethe content of MDA and NO in the kidney of diabetic rats. The improvementof pathological change in diabetic nephropathy also could contribute to thetreatment of the two drugs.3The mechanism of protective effects of DHI and metformin on thekidney of diabetic rats may be related to its anti-oxidation and improving theglomerulihyperfiltration. |
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