药物中断对慢性环孢素A肾毒性大鼠表皮生长因子表达的影响  

Effects of cyclosporine withdrawal on epidermal growth factor expression in chronic cyclosporine nephrotoxicity in rats

作　　者：王冲[1] 金英顺[1] 洪英礼[1] 刘雨田[1] 郑明楠[1] 崔镇花[1] 陈瑛[1] 李灿[1] 

机构地区：[1]延边大学附属医院肾内科,吉林延吉133000

出　　处：《延边大学医学学报》2010年第1期1-6,共6页Journal of Medical Science Yanbian University

摘　　要：[目的]观察停用环孢素A对慢性环孢素A肾中毒大鼠体内表皮生长因子(EGF)表达的影响.[方法]皮下注射给予SD大鼠环孢素A 5周,建立慢性环孢素A肾毒性后,停用环孢素A观察5周和10周;另设正常对照组,皮下注射给予橄榄油.检测各组大鼠体重、收缩期血压、血清肌酐及肌酐清除率;以PAS染色和三色染色观察肾组织病理改变.用免疫印迹法及免疫组织化学染色检测EGF蛋白的表达和分布.[结果]与对照组比较,慢性环孢素A肾毒性组大鼠体重明显减轻,血肌酐显著上升,肌酐清除率明显下降,入球动脉发生玻璃样病变,肾小管间质带状纤维化,EGF蛋白表达明显减少.停用环孢素A可见上述各项指标发生逆转.EGF蛋白的表达随药物中断时间发延长而呈阶梯状增加,且与肾小管间质带状纤维化程度呈负相关(r=-0.848).[结论]停用环孢素A可上调EGF的表达,且呈时间依赖性,而EGF的高表达与改善肾小管间质带状纤维化相关.OBJECTIVE To investigate the effects of cyclosporine（CsA） withdrawal on epidermal growth factor（EGF） expression in chronic CsA nephrotoxicity.METHODSChronic CsA nephrotoxicity in SD rats was induced by subcutaneous injections with the CsA for 5 weeks,and then withdrawing it for 5 or 10 weeks.The control group was subcutaneously injected with olive oil.Body weight,systolic blood pressure（SBP） and renal function（SCr,Ccr） were detected,pathologic changes of kidney were observed with PAS and trichrome staining,and expression and distribution of EGF protein was estimated by using immunohistochemistry and immunoblotting.RESULTSAs compared with control group,it was showed in chronic CsA nephrotoxicity of rats that loss of body weight,increased of SCr and Ccr,hyaline degeneration of afferent glomerular arteriole,tubulointerstitial fibrosis,and decreased of EGF expression.After CsA withdrawal,these parameters were significantly reversed,and the expression of EGF protein was dramatically increased with the time elongation of CsA withdrawal and negatively correlated with the degree of tubulointerstitial fibrosis score（r=-0.848）.CONCLUSIONThe CsA withdrawal could up regulate the EGF expression as an time dependence,and overexpression of EGF is correlated with improving renal tubulointerstitial fibrosis chronic CsA nephrotoxicity of rats.

关 键 词：表皮生长因子 亲环素类 中毒 肾 大鼠 

分 类 号：R595.4[医药卫生—内科学]