环孢霉素A抑制肾性高血压大鼠心肌肥大的作用机制  

The Mechanism By Which Cyclosporin A Inhibits Cardiac Hypertrophy in Renal Hypertension Rats

作　　者：常连庆[1] 谢晓华[1] 陈雯[1] 李朝晖 孙愚[1] 刘珍荣[1] 庞永正[2] 唐朝枢[2] 

机构地区：[1]中国人民解放军总医院南四科,北京100853 [2]北京大学人民医院,北京100853

出　　处：《高血压杂志》2004年第3期249-252,共4页Chinese Journal of Hypertension

基　　金："十五"军队医药卫生科研基金重点课题资助 (0 2Z0 1 0 )

摘　　要：目的　观察环孢霉素A对肾性高血压大鼠心肌肥大的抑制作用 ,并探讨其作用机制。方法　 2 0只Wistar大鼠随机分为 3组 :两组采用一肾一夹模型制造肾性高血压 ,其中高血压组 (n =7)予生理盐水腹腔注射 ;CsA组 (n =7)给予环孢霉素A(CsA) 5mg·kg- 1 ·d- 1 腹腔注射 ;假手术组 (n =6)只给予生理盐水腹腔注射。称重法测定心重比 ,发色底物法测CaN活性 ;半定量PCR测定各组心肌组织中心房利钠因子 (ANF)及CaNmRNA的水平 ,同时用免疫组织化学染色方法 ,观察心肌中CaN及活化T细胞核因子 (nuclearfactorofactivatedTcell,NFAT)的表达。结果　肾性高血压大鼠经CsA干预 4周 ,其心重比较未干预组明显降低 (P <0 0 5 ) ,ANFmRNA水平较手术组明显降低 (P <0 0 5 ) ,与假手术组水平接近 ,心肌肥大受到抑制 ,同时发现心肌中CaN活性较未干预组显著下降 ,CaNmRNA水平较手术组明显降低 (P <0 0 5 ) ,免疫组化显示CsA干预组心肌中CaN及NFAT表达降低。Objective To determine the mechanism by which Cyclosporin A(CsA) inhibits calcineurin(CaN)-dependent cardiac hypertrophy in renal hypertension rats. Methods The model of renal hypertension rats were established by the operation of “one kidney one clip(1K1C)”. Twenty Wistar rats were divided into 3 groups randomly: ①Hypertension group(n=7): 1K1C+0.9% NaCl 1 mL·kg -1·d -1 intraperitoneally and 0.9%NaCl in drinking of water for 4 weeks; ②CsA group(n=7):1K1C+CsA 5 mg·kg -1·d -1 intraperitoneally and 0.9% NaCl in drinking 4 weeks; ③sham operation group(n=6): sham operation +0.9% NaCl 1 mL·kg -1·d -1 intraperitoneally and in drinking for 4 weeks. The ratio of left ventricle weight to body weight(LW/BW) and the activity of CaN in the cardiac tissue were measured. Half quantitative PCR was employed to determine the levels of atrial natriuretic factor(ANF) mRNA and CaN mRNA in cardiac tissue. The expressions of CaN and NFAT (nuclear factor of activated T cell ) in cardiac tissue were examined by immunohistochemical staining. Results The ratio of LW/BW and activity of CaN in CsA group was decreased significantly compared with untreated group (LW/BW:0.27%±0.03% vs 0.35%±0.06%,P<0.05;CaN: 0.18±0.05 A410/mg protein vs 0.44±0.11 A410/mg protein, P<0.05). CaN and ANF mRNA level in CsA group was similar with that of sham operation group and much lower than that in untreated group(P<0.05). In CsA group, the lower expression of CaN and NFATc3 in cardiac tissue was also shown. Conclusion The preventive mechanism of CsA cardiac hypertrophy is related to the decrease of CaN expression and its activity in cardiac tissue.

关 键 词：高血压 肾性 左心室肥大 环孢霉素A 磷酸单酯水解酶类 

分 类 号：R544.1[医药卫生—心血管疾病]