西拉普利、氯沙坦对尿酸肾病大鼠肾上皮细胞生长因子(EGF)和成纤维细胞生长因子(bFGF)mRNA表达的影响

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目的 探讨西拉普利 (cilazapril)和氯沙坦 (losartanpotassium)对尿酸肾病大鼠肾小管上皮细胞生长因子 (EGF)和成纤维细胞生长因子 (bFGF) ,受体 (EGFR ,FGFR)及胶原ⅢmRNA及蛋白质表达的影响。方法  4 0只腺嘌呤致尿酸肾病大鼠 ,3周后分组 ,1组为模型对照组 10只 ;1组为西拉普利治疗组 12只 (10mg/kg·d一次性灌胃 ) ;另 1组为氯沙坦治疗组 12只 (4 0mg/kg·d一次性灌胃 ) ;对照组 6只 ;药物治疗 4周后麻醉 ,心脏采血之后处死大鼠 ;取肾组织固定、包埋、切片后行原位杂交及免疫组化检测EGF ,bFGF ,EGFR ,FGFR及胶原Ⅲ表达。 结果 尿酸肾病模型组肾小管上皮细胞 ,间质EGFmRNA和bFGF蛋白质广泛表达 ,同时发现肾小管 ,肉芽肿内单个核细胞及间质成纤维细胞广泛表达EGFR ,FGFR及三型胶原。而西拉普利和氯沙坦治疗组EGFmRNA表达下调 ,bFGF蛋白表达也下调 ,并且主要在肾小管上皮细胞有表达。EGFR的表达治疗组同模型组比较稍有减少 ;而FGFR治疗组同模型组比较差异不明显 ;三型胶原表达只在氯沙坦组明显下调。 结论 实验性尿酸肾病模型中EGF ,bFGF在肾内广泛表达 ,西拉普利和氯沙坦能下调EGF ,bFGF ,EGFR(轻度 ) ,只有氯沙坦组下调三型胶原表达 ,因此得出EGF ,bFGF在尿酸肾病发病过程中发挥重要作用 ,并且 Objective To investigate the effects of cilazapril and losartanpotassium on renal tubule epithelial growth factor (EGF), fibroblast growth factor (bFGF), receptor (EGFR, FGFR) and collagen Ⅲ mRNA in rats with uric acid nephropathy And protein expression. Methods 40 rats with uric acid and nephropathy induced by adenine were divided into three groups after one week. One group was model control group, the other one group was treated with cilazapril 12 (10mg / kg · d) One group was treated with losartan 12 rats (40 mg / kg · d once); 6 rats in the control group were anesthetized after 4 weeks of drug treatment and blood was collected from the heart. Rats were sacrificed and the kidneys were fixed, After in situ hybridization and immunohistochemistry, the expressions of EGF, bFGF, EGFR, FGFR and collagen Ⅲ were detected. Results The expression of EGFR and bFGF protein in renal tubular epithelial cells and interstitial fibroblasts in uric acid nephropathy model group was extensively expressed. In addition, EGFR, FGFR and type III collagen were widely expressed in tubules, granulomas and mesenchymal fibroblasts. However, the expression of EGFmRNA in cilazapril and losartan treatment groups was down-regulated while the expression of bFGF protein was down-regulated, which was mainly expressed in renal tubular epithelial cells. The expression of EGFR in the treatment group was slightly reduced compared with the model group, while the difference between the FGFR treatment group and the model group was insignificant. The expression of type III collagen was only down-regulated in the losartan group. Conclusions EGF and bFGF are widely expressed in the kidney in experimental model of uric acid nephropathy. Cilazapril and losartan can down-regulate EGF, bFGF and EGFR (mild), only losartan can down-regulate type III collagen expression. Therefore EGF , bFGF play an important role in the pathogenesis of uric acid nephropathy, and
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