乌司他丁对糖尿病大鼠的肾脏保护作用及其机制

目的观察乌司他丁(UTI)对糖尿病大鼠肾脏的保护作用,并探讨其可能的机制。方法 Wistar大鼠30只,随机选10只为空白对照组(A组),余20只大鼠采用腹腔注射链脲佐菌素成功构建糖尿病模型后,随机分为糖尿病组(B组)及UTI干预组(C组),每组10只。C组每日腹腔注射UTI 40 000 IU/kg,A组及B组每日腹腔注射等量生理盐水。分别于第8周及第12周检测各组大鼠的空腹血糖(FPG)、24 h尿白蛋白、血肌酐(SCr)及尿肌酐,并计算内生肌酐清除率(Ccr);制备肾匀浆,并检测血清及肾匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)、结缔组织生长因子(CTGF)、基质金属蛋白酶-9(MMP-9)及纤溶酶原激活物抑制剂-1(PAI-1)的含量。结果①B、C组FPG高于A组(P均<0.05),C组与B组间差异无统计学意义(P>0.05);②B、C组24 h尿白蛋白、SCr高于A组,C组低于B组(P均<0.05);③B、C组Ccr低于A组,C组高于B组(P均<0.05);④B、C组血清及肾匀浆MDA、CTGF及PAI-1含量均高于A组,C组低于B组(P均<0.05);⑤B、C组血清及肾匀浆SOD及MMP-9均低于A组,C组高于B组(P均<0.05)。结论 UTI对糖尿病大鼠肾功能具有保护作用,其机制可能与降低糖尿病大鼠MDA、CTGF及PAI-1表达、升高SOD及MMP-9表达,降低尿蛋白等因素有关。

Protective effects and mechanisms of ulilnastatin against renal injury in rats with diabetic nephropathy

Objective To investigate protective effects of ulilnastatin(UTI) on kidneys of diabetic rats and its mechanisms.Methods 10 rats were randomly selected from 30 Wistar rats as the control group(group A).The remaining 20 rats injected with streptozotocin(STZ) were randomly divided into the diabetic group(group B) and the UTI group(group C),10 rats in each group.Rats in group C were intraperitoneally administered UTI at a dose of 40 000 IU/kg,and rats in groups A and B were intraperitoneally administered the same volume of normal saline.At the 8th and 12th weeks,fasting blood glucose(FPG),urine creatinine and serum creatinine(SCr) were detected,24h urine was collected,the albumin was detected,and creatinine clear rate(Ccr) was calculated.Nephridial tissue homogenate was made and malondialdehyde(MDA),superoxide dismutase(SOD),connective tissue growth factor(CTGF),matrix metallopeptidase-9(MMP-9) and plasminogen activator inhibitor-1(PAI-1) in serum and nephridial tissue homogenate were detected.Results ① FBG in groups B and C was obviously more increased than in group A(P<0.05),while there was no significant difference between group C and group B(P>0.05).② 24h urinary albumin and Scr were obviously more increased in groups B and C than in group A(P<0.05),and they were obviously more decreased in group C than in group B(P< 0.05).③ Ccr in groups B and C was obviously more decreased than in group A(P<0.05),and that in group C was obviously more increased than in group B(P<0.05).④ In contrast to group A,MDA,CTGF and PAI-1 in groups B and C were obviously more increased(P<0.05),and those in group C were obviously more decreased than group B(P<0.05).⑤ SOD and MMP-9 in groups B and C were obviously more decreased than in group A(P<0.05),those in group C were obviously more increased than in group B(P<0.05).Conclusion UTI exerts protective effects on renal function of diabetic rats,and the mechanism of this action is related to decreases of urinary albumin,MDA,CTGF and PAI-1,and increases of SOD and MMP-9.