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  

The Effect of Cilazapril and Losartan on Renal EGF and bFGF mRNA Expres sion in Uric Acid Nephropathy Rats

作　　者：郝丽荣[1] 吕松岑[2] 宫本源[3] 解汝娟[1] 邸波[1] 黄淇[4] 

机构地区：[1]哈尔滨医科大学第一临床医学院肾内科,黑龙江哈尔滨150001 [2]哈尔滨医科大学第一临床医学院附属第二医院,黑龙江哈尔滨150001 [3]呼兰第一人民医院,黑龙江哈尔滨150001 [4]呼兰第一人民医院病理教研室,黑龙江哈尔滨150001

出　　处：《高血压杂志》2004年第5期436-441,共6页Chinese Journal of Hypertension

基　　金：黑龙江省自然基金资助 (D973 0 )

摘　　要：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 。Objective To study the effect of angiotensin-convertin g enzyme inhibitor (Cilazaprril) and angiotensin Ⅱ type 1 receptor antagonist ( Losartan potassium) on the expression of EGF and bFGF growth factor in experimen tal uric acid nephropathy. Methods Uric acid nephropathy rats were established by feeding adenine for 3 weeks. Rats were divided into 4 grou ps: model control groups 10 rats; cilazapril group 12 rats(received 10 mg/kg·d ); losartan groups 12 rats (received 40 mg/kg·d); control group 6 rats. 4 weeks later, rats were sacrificed. SABC immunohistochmical staining and in situs hyb ridization technique were used to investigate EGF, EGFR, bFGF, FGFR and collagen Ⅲ in renal tissue. ResultsIn uric acid nephropathy mode l, EGF mRNA and bFGF protein were expressed in the renal tubular cells and inter stitium. EGFR and collagen III were expressed wildly in renal tubular ce lls, mononuclear cells in granuloma and interstitium fibroblasts. Cilazapril and losartan down regulated EGF mRNA and bFGF.However collagen Ⅲ expression was down-regulated exclusively by losartan.Conclusion EGF and bFGF may be associated with the progress of u-ric nephropathy and expressed predo minately in tubulointerstitial inflammation and fibroblasts.ACE-I and ARB decreased synthesis of extracellular matrix and interstitial fibrosis by do wn regulating EGF, bFGF expression.

关 键 词：生长因子 成纤维细胞生长因子 mRNA 表达 尿酸肾病 

分 类 号：R692[医药卫生—泌尿科学]