| 摘要: |
| \[摘要\]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-Dawley大鼠皮下注射CsA(15 mg·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±7 vs 13±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。 |
| 关键词: 慢性环孢素A肾毒性 间质性肾炎；血管紧张素Ⅱ 血管紧张素受体 |
| DOI：10.3724/SP.J.1008.2010.01286 |
| 投稿时间：2010-05-20修订日期：2010-11-26 |
| 基金项目: |
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| Expression of angiotensin Ⅱ and its receptors in a rat model of chronic cyclosporine nephrotoxicity |
| JIN Ying-shun, HONG Ying-li, CUI Zhen-hua, LIU Yu-tian, JIN Hai-feng, JIN Hua, CHEN Ying, LI Can* |
| (Nephrology and Dialysis Unit, Department of Internal Medicine, the Affiliated Hospital of Yanbian University, Yanji 133000, Jilin, China) |
| Abstract: |
| \[Abstract\]ObjectiveTo observe the expression of angiotensinⅡ(AngⅡ) and its receptors in a rat model of chronic cyclosporine (CsA) nephrotoxicity. MethodsChronic 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. ResultsCompared 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). ConclusionThe 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. |
| Key words: chronic cyclosporine nephrotoxicity interstitial nephritis angiotensin Ⅱ angiotensin receptors |
