目的:探讨复方鳖甲软肝方对阿霉素肾病大鼠肾组织的保护作用机制。方法:将45只大鼠随机分为3组,正常对照组(9只)、假手术组(9只)及手术组(27只)。切除大鼠右侧肾脏并腹腔注射阿霉素建立阿霉素肾病大鼠模型。于术后1周,手术组按体重再次随机均分为模型组、苯那普利组和复方鳖甲软肝方组。从开始注射阿霉素后,苯那普利组(25mg/kg)和复方鳖甲软肝方组(14g/kg)开始灌胃治疗,假手术组给予等量生理盐水灌胃。观察并记录实验2、4、6、8和10周大鼠体重、24h尿蛋白;于10周末处死大鼠,取大鼠颈动脉血检测尿素氮、血肌酐、胆固醇、甘油三酯、总蛋白和白蛋白;观察肾组织病理形态学改变,采用免疫组化及原位杂交方法分析肾组织ET-1蛋白及其mRNA表达。结果:除正常对照组和假手术组外,其余3组大鼠均有不同程度的摄食减少、精神不振、活动迟缓、尿量减少、体重减轻、24h尿蛋白定量增高、血生化指标异常等,而苯那普利组和复方鳖甲软肝方组均有不同程度改善,且复方鳖甲软肝方组优于苯那普利组,但两者差异无显著性。模型组大鼠肾小管上皮细胞、肾小球系膜细胞以及肾小球脏层上皮细胞胞浆中ET-1蛋白及mRNA表达呈强阳性;复方鳖甲软肝方组与苯那普利组大鼠肾组织ET-1蛋白及mRNA表达均较模型组显著减少,但两者比较差异无显著性。结论:复方鳖甲软肝方能够减少阿霉素肾病大鼠肾小管上皮细胞、肾小球系膜细胞以及肾小球脏层上皮细胞胞浆中ET-1蛋白及其mRNA表达,降低肾组织ET-1含量,从而起到保护肾功能,延缓肾功能衰竭的作用。
To explore the protective effect of compound Biejia Ruan'gan prescription (复方鳖甲软肝方) on kidney tissues of rats with adriamycin (Adr) nephropathy. Methods: Forty-five rats were randomly divided into three groups: normal control group (n=9), sham operation group (n= 9) and surgical group (n= 27). The models with Adr nephropathy were established by the reduplication of right kidney excision and intraperitoneal injection of Adr in rats. According to the body weight, the surgical group was subdivided into three groups (n= 9): the model group, henazepril group and compound Biejia Ruan'gan prescription group. At the beginning of the injection of Adr, the gastric lavage of benazepril (25 mg/kg), compound Biejia Ruan'gan prescription (14 g/kg) and equal amount of normal saline was carried out in the benazepril, compound Biejia Ruan'gan prescription and sham operation groups respectively. The weight and 24 hours urinary protein of rats 2, 4, 6, 8 and 10 weeks after experiment were observed and recorded. Ten weeks after treatment, the rats were sentenced to death, the blood was taken from the carotid artery. The blood urea nitrogen, serum creatinine, cholesterol, triglyeride, total protein and albumin were determined. Renal pathomorphologic changes were observed, ET - 1 protein and mRNA expressions were measured by immunohistochemical and hybridization in situ method. Results : In the model group, the expressions of ET - 1 protein and mRNA were strongly positive in the cytoplasma of renal tubular epithelial, mesangial and glomerular splanchnoderm epithelial cells, while in the compound Biejia Ruan'gan prescription group and benazepril group were markedly less in the kidney tissues, the comparison being statistically significant (all P〈0.05). Conclusion: Compound Biejia Ruan'gan prescription can protect the renal function and delay the occurrence of renal failure in rats with Adr nephropathy by diminishing ET - 1 protein and mRNA expression and the ET -