摘要
目的:探讨血管紧张素转换酶抑制剂苯那普利对糖尿病大鼠肾脏病变的保护作用及其机制。方法:24只健康雄性Wistar大鼠随机分成正常对照组(NC组,n=8)、糖尿病未治疗组(DM组,n=8)和糖尿病苯那普利治疗组(DL组,n=8)。应用链脲佐菌素(STZ)诱导糖尿病模型,造模成功后,用苯那普利10 mg/(kg.d)对DL组进行治疗性灌胃,其余2组均用等量自来水灌胃。4周后,将所有大鼠一次性处死,摘取肾脏。用明胶酶谱分析法检测肾组织基质金属蛋白酶-2(MMP-2)活性;用免疫组化法检测肾组织IV胶原(IV-C)、MMP-2、基质金属蛋白酶组织抑制因子-2(TIMP-2)蛋白的表达,并利用计算机图像分析系统进行半定量图像分析;用逆转录-聚合酶链反应测定肾组织中MMP-2、TIMP-2mRNA的表达。同时进行肾组织透射电镜检查。结果:糖尿病组与正常对照组比较,尿量、Upro、BUN、Ccr显著增高(P均<0.01),肾小球MMP-2活性、mRNA及蛋白表达均降低,而TIMP-2 mRNA及蛋白表达升高,IV-C胶原表达亦增加;苯那普利治疗组Upro、BUN、Ccr较糖尿病组均有不同程度的降低(P均<0.05),肾小球MMP-2活性、mRNA及蛋白表达升高,而TIMP-2 mRNA及蛋白表达I、V-C胶原表达均减少。结论:苯那普利对糖尿病大鼠肾功能和肾组织形态学具有保护作用,其作用机制可能与上调肾小球MMP-2的表达和下调TIMP-2的表达,提高MMP-2活性,从而减轻肾小球细胞外基质沉积有关。
Objective： To investigate the protective effect and possible mechanisms of benazepril on diabetic nephropathy（DN）in rats. Methods： Twenty-four healthy male Wistar rats were randomly divided into normal control group （NC group）, diabetic group untreated with benazepril （DM group） and diabetic group treated with benazepril （DL group）. The DN model was established following intraperitoneal injection of streptozecin （60 mg·kg^-1 ）. Benazepril （ 10 mg·kg^-1·d^-1 ） was given to the DL group for 4 weeks, whereas the same milliliter water was given to the other two groups. At the end of 4 weeks, renal function was evaluated with 24-hour urinary protein （Upro）, clearance of ereatinin （Cer） and blood urea nitrogen （BUN）, the MMP-2 activities were determined by gelatin zymography, the expression levels of MMP-2, TIMP-2 and collagen Ⅳ （Ⅳ-C） protein in the kidney tissues were determined by immunohistochemistry method and the gene expressions of MMP-2 and TIMP-2 were measured by RTPCR. Results： Compared with NC group, DM group had an increase of serum BUN, Upro and Cer values, a decrease of mRNA and enzymatic activity and proteins of MMP-2 but an increase of the Ⅳ-C and TIMP-2 expressions. All the diabetes-associated changes in renal function and MMP/TIMP were attenuated by benazepfil treatment with reduced Ⅳ-C accumulation. Conclusion： Benazepfil has some protective effect on diabetic nephropathy, which may relate with the inhibition of excessive deposition of glomeruli extracellular matrix by up-regulating the MMP-2 and downregulating the TIMP-2 expressions.
出处
《山东大学学报（医学版）》
CAS
北大核心
2006年第4期404-409,共6页
Journal of Shandong University:Health Sciences
基金
山东省自然科学基金资助课题(Y2002C35)
