摘要
目的观察血管紧张素Ⅱ(AngⅡ)及其受体在慢性环孢素A(CsA)肾毒性中的表达。方法 Sprague-Daw-ley大鼠皮下注射CsA(15mg·kg-1.d-1)4周,建立慢性CsA肾毒性模型;正常对照组皮下注射橄榄油。检测各组大鼠的体重、收缩期血压、血CsA浓度、血清肌酐、肌酐清除率;三色染色观察肾小管间质纤维化;免疫组织化学染色和蛋白质免疫印迹法分别检测AngⅡ及其受体AT1和AT2的表达。结果慢性CsA肾毒性组表现为体重减少、血肌酐上升、肌酐清除率下降、肾小管间质带状纤维化(P<0.01)。与对照组相比,毒性组大鼠AngⅡ的免疫活性明显增加(47±7vs13±4,P<0.01),主要分布于入球动脉的肾小球旁器,与肾小管间质纤维化程度紧密相关(r=0.769,P<0.001)。免疫印迹显示毒性组AngⅡ受体AT1的表达明显减少[(114±14)%vs(42±6)%,P<0.01],而AT2的表达增加[(129±23)%vs(469±43)%,P<0.01]。结论在慢性CsA肾毒性中,肾内肾素血管紧张素被激活,表现为AngⅡ免疫活性增加,这种AngⅡ免疫活性与肾小管间质纤维化紧密相关。
Objective To observe the expression of angiotensinⅡ（AngⅡ） and its receptors in a rat model of chronic cyclosporine （CsA） nephrotoxicity.Methods Chronic CsA nephrotoxicity was induced in Sprague-Dawley rats by administering CsA （15 mg/kg s.c.） for 4 weeks.The body weight,systolic blood pressure,serum CsA,serum creatinine （Cr）,and creatinine clearance rate （Ccr） of rats were examined in each group.Trichrome staining was used to observe the tubulointerstitial fibrosis; expressions of AngⅡ and its receptors （AT1 and AT2） were examined by immunohistochemical staining and Western blotting analysis.Results Compared with the control rats,CsA-treated rats showed decreased body weight,increased Cr,decreased Ccr and tubulointerstitial fibrosis （P〈0.01）.Immunohistochemistry revealed that the immunoreactivity of AngⅡ was significantly increased in the CsA-treated rats （47±7 vs 13±4,P〈0.01）,with the immunoreactivity mainly locating to the juxtaglomerular afferent arterioles,and the immunoreactivity was significantly correlated with tubulointerstitial fibrosis （r=0.769,P〈0.001）.Western blotting analysis showed significantly decreased AT1 expression （[114±14]% vs [42±6]%,P〈0.01） and increased AT2 expression （[129±23]% vs [469±43]%,P〈0.01）.Conclusion The findings of our study suggest that the intrarenal renin-angiotensin system is activated during chronic CsA nephrotoxicity,which is manifested by increased AngⅡ immunoreactivity,and this increased immunoreactivity is closely related to tubulointerstitial fibrosis.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2010年第12期1286-1290,共5页
Academic Journal of Second Military Medical University
