Protective Effects And Mechanisms Of Ulilnastatin On Renal Injury In Rats With Diabetic Nephropathy

Backgroud and Objective:Diabetic nephropathy is a major etiology of end-stage renal disease, and it is also one of the serious chronic microvascular complications of diabetes mellitus, it is a serious threat to human health. So it is important to explore the pathogenesis mechanisms of DN and find early preventing drugs. The occurrence mechanisms and preventive measures has become a current research focus. The pathogenesis of DN which is complex hasn’t been fully clarified. With the in-depth study, it is fonud that DN is induced by genetic factors, hemodynamic changes, non-enzymatic glycosylation, polyol pathway activation, oxidative stress, vasoactive substances and cytokines, protein kinase C activation and kidney disease protein. Studies have confirmed that ulilnastatin has the effects of antioxidation, anti-micro-inflammation, improving circulation, Protection of the liver, kidney and other vital organs. It has been a good application In acute and critically ill patients with organ protection. Recent studies have revealed its role in peritoneal fibrosis and other chronic diseases. But there is no study confirmed if UTI has a protective effect on DKD. Therefore, in this study, we copy the DN rat model, and observe the role of UTI in DN rats, further investigate the mechanism from aspects of antioxidation, anti-renal fibrosis and anti-glomerular sclerosis.Methods:1. Model and experimental grouping:30wistar rats(SPF, male) were housed in cages and fed standard pellet diet. DM was induced by a single intraperitoneal injection of streptozotocin(STZ,60mg/kg body weight) diluted in citrate buffer(0.1mmol/L, pH4.5). Select the20diabetic rats and randomly divided into diabetic group (group B) and UTI group (group C), and set the same batch of10normal rats as control group(group A). The rats of group C were received intraperitoneal injection of UTI40000IU/kg dail, the rats of group A and B were received intraperitoneal injection of saline daily,12weeks in a row.2. Specimen Collection:Rats in each group were dealed with in the eighth and twelfth week and Collected the urine and blood, prepared Renal biopsy and albumi.3. Detection index:Blood was collected for FBG。Serum creatinine and Urine creatinine were detected by BeckmanCX-5Biochemical analyzer, and calculated the Ccr(ml/min).Detected24h urinary protein, MDA, SOD, CTGF, MM-9, PAI-1. kidney tissue was studied by HE staining and Immunohistochemical.Results:1. In the eighth and Twelfth week, FBG of group B and C were obviously increased than group A(P<0.05), but there were no significant difference between group C and group B(P>0.05).24-h urinary albumin and Scr of group B and C were obviously increased than group A(P<0.05), group C were obviously decreased than group B(P<0.05). Ccr of group B and C were obviously decreased than group A(P<0.05), group C were obviously increased than group B(P<0.05).2. In the eighth and Twelfth week, there were significant differences among MDA and SOD of every group(P<0.05). In contrast to group A, the MDA of group B and C were obviously increased(P<0.05); group C were obviously decreased than group B(P<0.05). SOD of group B and C were obviously decreased than group A (P<0.05), group C were obviously increased than group B(P<0.05).3. In contrast to group A, the CTGF of group B and C were obviously increased(P<0.05). The CTGF of group C were decreased than group B(P<0.05).4. Compared with group A, the PAI-1of group B and C were obviously increased(P <0.05); group C were obviously decreased than group B(P<0.05). MMP-9of group B and C were obviously decreased than group A(P<0.05), group C were obviously increased than group B(P<0.05).5. kidney tissue in the group A were normal by light microscope. In group B, we could observe that glomerular volume and mesangial area were increased significantly, renal tubular were swelled. In Group C, the changes were significantly reduced compared with group B.6. CTGF immunohistochemical staining:The coloration of group A was pale sparse, and that of group B was widely and thick. Compared with group B, the coloration was thiner.7. MMP-9:The coloration of group A was obviously, group B was significantly reduced, and group C was thicker than group B, but thiner than group A. PAI-1: Expression of group A was not obviously, group B was increased, and group C was reduced.Conclusion:1. UTI could be significantly lower Scr, increased Ccr, lower24h urinaryprotein in diabetic rats. UTI provide protective effects to renal function of diabetic rats.2. UTI could reduce kidney damage in diabetic rats by antioxidation.3. UTI could delay the the development of DKD by reducing CTGF.4. UTI could reduce PAI-1levels, elevate MMP-9content, thereby reducing ECM deposition, Inhibiting the progression of renal disease.