肾素血管紧张素系统激活在环孢霉素A肾病中的作用

Role of activation of renin angiotensin system in cyclosporine A nephropathy

目的 :探讨肾素血管紧张素系统 (RAS)的激活在环孢霉素 A (Cs A)肾病中的作用。方法 :低盐饮食大鼠皮下注射 Cs A(1 5 mg· kg- 1· d- 1 ) 2 8d制成 Cs A肾病模型。 Cs A肾病大鼠分别胃内灌入自来水、盐酸维拉帕米、依那普利 ,剂量均为 1 0 m g· kg- 1· d- 1。采用放射免疫法检测各组实验动物血管紧张素 (Ang )水平 ;Northern杂交检测肾组织血管紧张素 1型受体 (AT1 R) m RNA的表达 ,同时对各组实验动物肾间质纤维化程度进行半定量计分。结果 :Cs A处理组血浆和肾组织 Ang 水平为 (4 92± 92 ) ng/L 和 (2 9.8± 6 .0 ) ng/g,均明显高于对照组 (1 90± 36 ) ng/L和 (8.7± 1 .7) ng/g,P均 <0 .0 0 1 ;而依那普利可以明显降低血浆和肾组织 Ang 水平 (P均 <0 .0 5 )。 Cs A处理后出现明显的肾间质纤维化 ,依那普利能明显减轻肾间质纤维化 ,盐酸维拉帕米对肾间质纤维化无显著改善。结论 :RAS的激活在 Cs A肾间质纤维化过程中起重要作用 ,阻断 RAS可以明显减轻 Cs A引起的肾间质纤维化。

Objective: To investigate the role of renin angiotensin system(RAS) activation in cyclosporine A nephropathy. Methods: Rats were fed with low salt diet. After seven days, they were randomly divided into four groups: vehicle ( n= 7), CsA treated ( n= 7), CsA+verapamil ( n= 7), CsA+enalapril ( n= 7).All rats except vehicle received a daily subcutaneous injection of CsA (15 mg/kg)for four weeks. Plasma and renal tissue angiotensinⅡ(Ang Ⅱ) levels were measured by radioimmunoassay. The expression of angiotensin Ⅱtype 1 receptor (AT1R) was examined by Northern blot. Results: Plasma and renal tissue angiotensin Ⅱ levels were significantly elevated in CsA treated rats when compared to that in vehicle rats〔(190±36)ng/L vs. (492±92)ng/L, (29 8±6 0)ng/g vs. (8 7±1 7)ng/g, P <0 001〕. Enalapril reduced angiotensin Ⅱ levels significantly (both P <0.05). The expression of AT1R mRNA was downregulated by CsA, this down regulation was reversed by enalapril. CsA treated animals showed marked tubulointerstitial fibrosis , enalapril lessened the tubulointerstitial fibrosis significantly( P <0 05). Verapamil did not improve tubulointerstitial fibrosis significantly( P >0 05). Conclusion: RAS activation plays an important part in CsA nephropathy. Blockade of RAS may retard the progression of tubulointerstitial fibrosis caused by CsA.