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Title:: Cyclosporine A inhibits tissue calcineurin activity in vital organs of renal hypertensive rats

作者:: 陈雯¹; 谢晓华¹; 常连庆¹; 李晓玲¹; 刘宁²; 刘秀华¹; 1.解放军总医院南楼综合科,北京 100853；2.解放军272医院,天津

Author(s):: CHEN Wen; XIE Xiao-hua; CHANG Lian-qing; LI Xiao-ling; LIU Ning; LIU Xiu-hua; General Hospital of PLA, Beijing 100853, China

关键词:: 高血压; 钙调神经磷酸酶; 环孢霉素A

Keywords:: hypertention; calcineurin; cyclosporine A

分类号:: R541.3

DOI:: -

文献标识码:: A

摘要:: 目的研究一肾一夹肾性高血压大鼠组织钙调神经磷酸酶（calcineurin，CaN）活性变化及环孢霉素A(Cyclosporine A ，CsA)的调控作用。方法取20只Wistar 大鼠随机分为3组：假手术组（n=6），一肾一夹手术组（n=7）和CsA干预组（n=7）。采用放免法测定血浆血管紧张素Ⅱ（angiotensinⅡ，AngⅡ）、醛固酮（Aldosterone ，Ald）和内皮素（endothelin ，ET-1）浓度，采用比色测定一氧化氮（NO）浓度。以PNPP为底物测定术后4周大鼠各组织器官CaN活性。结果肾性高血压大鼠心脏、脾、肾脏、肺、脑CaN活性较假手术组显著升高（均P<0.05）,干预组上述组织器官CaN活性较手术组显著下降（P<0.05）。肾性高血压大鼠组肝脏CaN活性较假手术组显著下降, 环孢霉素A干预组肝细胞CaN活性较手术组继续显著下降（P<0.05）。各组大鼠主动脉中CaN活性无明显变化。各组大鼠血浆Ald、AngⅡ、ET-1及NO浓度亦无明显变化。结论肾性高血压大鼠心、脑、肾、脾、肺脏组织CaN活性均显著升高， CsA对肾性高血压大鼠上述各组织脏器CaN活性具有广泛的抑制作用。

Abstract:: AIM To investigate the activity of calcineurin (CaN) and its sensitivity to cyclosporine A (CsA)induced inhibition in renal hypertensive rats (RHRs). METHODS The rat model of renal hypertensive was established by the onekidney and oneclip（1K1C）operation of the right nephrectomy and chronic partial occlusion of left renal artery. Twenty male rats were divided into 3 groups randomly: sham operation group (sham op group, n=6): sham operation + 9 g/L NaCl 1 ml/(kg·d) intraperitoneally and drinking tap water for 4 weeks. 1K1C hypertension group(op group, n=7)：1K1C operation + 9 g/L NaCl 1 ml/(kg·d) intraperitoneally and drinking 9 g/L NaCl for 4 weeks. CsA group (CsA group, n=7): 1K1C operation +CsA 5 mg/(kg·d) intraperitoneally and drinking 9 g/L NaCl for 4 weeks. The plasma concentrations of Aldosterone（Ald）, angiotensinⅡ(Ang Ⅱ) and endothelin (ET-1) were detected by the radioimmunoassay. NO was detected by the nitrate assay. CaN activity was measured by using PNPP as substrate. RESULTS Compared with sham op group, CaN activity in heart, spleen, kidney, lung and brain of op group rats was increased significantly (P<0.05). CsA decreased CaN activity in theses organs significantly (P<0.05). CaN activity in liver of RHRs was decreased remarkably (P<0.05), which was further decreased significantly in CsAtreated rats (P<0.05). CaN activity in aorta of three groups showed no significant differences. The plasma concentrations of Ald， Ang Ⅱ， ET-1 and NO of three groups did not differ significantly. CONCLUSION CaN has a wide tissue distribution in 1K1C RHRs . Compared with sham operation group, there is a significant increase in CaN activity in heart, spleen, kidney, lung and brain of RHRs, which is inhibited remarkably by CsA.

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