苯那普利对糖尿病大鼠肾小球MMP-9影响的实验研究

EXPERIMENTAL STUDY OF THE EFFECT OF BENAZEPRIL ON MMP-9 PROTEIN EXPRESSION IN DIABETIC RATS RENAL CORPUSCULUM

目的探讨苯那普利对糖尿病大鼠肾小球基质金属蛋白酶-9(MMP-9)表达的影响。方法将雄性SD大鼠30只,随机抽出10只动物作为正常对照组(C组),其余20只采用腹腔注射STZ制备糖尿病大鼠模型。将这20只造模成功的糖尿病大鼠模型随机分为2组:糖尿病组(DM组)和药物处理组(DB组)。其中药物处理组即DB组大鼠每天应用苯那普利进行治疗性灌胃,C组和DM组用等量自来水灌胃。分别于治疗4、8周后,测定血糖和内生肌苷清除率,用代谢笼收集24h尿量。利用免疫组织化学染色及图像分析方法,对MMP-9在肾组织不同时间点的含量变化进行定性分析。结果苯那普利治疗组血糖水平和内生肌苷清除率明显降低,与糖尿病模型组相比有显著性差异。免疫组织化学染色显示:MMP-9在正常肾小球有阳性表达;DM组大鼠病程第8周时,MMP-9在肾小球表达明显减弱;DB组大鼠病程第8周时,经苯那普利治疗后,与同期糖尿病组比较表达明显上调。图像分析方法定量分析免疫组织化学染色阳性面积百分比,苯那普利治疗后第4周和第8周糖尿病肾病的大鼠肾小球MMP-9的阳性面积百分比分别为25.55%±3.44%和20.10%±2.11%,与糖尿病组对比有明显的提高(P<0.01)。结论MMP-9在糖尿病肾小球中的表达随病程进展逐渐减弱,苯那普利可能部分通过上调MMP-9在肾小球中的表达起到保护肾脏的作用。

Objective To investigate the effect of benazepril on the protein expression of matrix metalloproteinase-9 （MMP-9） in the renal corpusculum of diabetic rats. Methods 30 healthy adult SD rats were randomly divided into three groups： the normal control group （NC）, the diabetes mellitus model group （DM） and the benazepril-treated group （DB）, 10 in each group. Diabetes was induced in rats by injection with streptozozotocin （STZ）, and the rats in DB were treated with benazepril （50mg/kg/d） . The blood glucose, creatinine clearance rate （Ccr） and urinary volume of 24 hours were measured at 4 and 8 weeks of experiment. The level of MMP-9 in rat renal corpusculum was observed by immunohistochemistry and imag analysis. Results The blood glucose and Ccr in DB were obviously decreased compared with those of the DM group. Immunohistochemistry showed that positive expression of MMP-9 protein was observed in normal renal corpusculum cells, but it became weaker in DM rats and increased by the treatment of benazepril. The area percentage of immunohistochemical stain was significantly different between DM and DB. Conclusion MMP-9 expression is gradually weakend in the diabetic renal corpusculum as the disease progressing, and benazepril can increase the expression and activity of MMP-9 in the renal corpusculum so play an important role for protecting the kidney.