家兔慢性冬眠心肌血管紧张素和细胞外信号调节激酶的变化及药物干预的影响  

Changes of ATR and ERK1/2 in chronically hibernating myocardium of rabbits and influence of pharmaceutical interference

作　　者：李东野[1] 李薇薇[1] 夏勇[1] 张琳[1] 朱红[1] 徐通达[1] 钱文浩[1] 潘德峰[1] 

机构地区：[1]江苏徐州医学院附属医院心内科,徐州221002

出　　处：《中华老年心脑血管病杂志》2007年第11期758-761,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：江苏省高校自然科学研究计划项目(03KJB320145);徐州市科委资助课题(X2002036)

摘　　要：目的观察家兔慢性冬眠心肌(CHM)中血管紧张素Ⅱ(AngⅡ)1型受体(AT1R)、2型受体(AT2R)、细胞外信号调节激酶1/2(ERK1/2)的变化及药物对其的影响。方法64只家兔建立CHM模型后随机分为假手术组、对照组和卡托普利1、2组、美托洛尔1、2组和缬沙坦1、2组,每组8只。免疫印迹和免疫组织化学法检测AT1R、AT2R、ERK1/2表达的变化;TUNEL法测定心肌细胞凋亡;羟脯氨酸法测定间质胶原含量。结果CHM较正常心肌AT1R水平下降、AT2R水平上升,各药物组AT1R、AT2R较对照组下降(P<0.05);各组ERK1/2无明显变化(P>0.05);对照组双磷酸化细胞外信号调节激酶的含量较假手术组升高,各药物组较假手术组降低(P<0.05);3种药物均可抑制CHM间质纤维化、减少凋亡细胞。且药物大小剂量组间有显著性差异(P<0.05)。结论AT1R、AT2R、ERK1/2可能参与CHM的发生发展过程;卡托普利、缬沙坦和美托洛尔可能通过AngⅡ受体、ERK1/2途径发挥保护CHM的作用。Objective To observe the changes of angiotensin Ⅱ subtype 1 receptor（AT1R） ,angiotensin H subtype 2 receptor（AT2R） and extracellular signal regulated kinase 1/2 （ERK 1/2） in chronically hibernating myocardium（CHM） of rabbits and influnces of captopril, betaloc and valsartan. Methods Sixty-four rabbit models of chronically hiberating myocardium were randomly divided into shame operation group, control group,captopril group, betaloc group and valsartan group,with 8 rabbits in each group. The changes of AT~ R,AT2R and ERK 1/2 were assessed by Western blotting and immunohistochemistry. TUNEL was used to detect apoptosis of cardiomyocytes. Hydroxyproline method was used to measure collagen content in myocardial mesenchyme. Results The amount of AT1R reduced while AT2R increased in control group compared with sham group,and AT1R,AT2R reduced in drug groups compared with control group. The content of ERK 1/2 had no change in every group,while that of p-ERK was increased in control group compared with sham group, and was lower in drug intervention groups than control and sham groups. Three drugs could inhibit interstitial fibrosis and decrease apoptotic cells. The results of different doses of the drugs had statistical differences. Conclusions AT1R,AT2R and ERK 1/2 may participate in generation and evolution of CHM. Captopril,valsartan and betaloc may protect CHM through Ang H receptor-ERK1/2 pathway.

关 键 词：心肌顿抑 受体 血管紧张素 1型 受体 血管紧张素 2型 细胞外信号调节MAP激酶类 细胞凋亡 

分 类 号：R541[医药卫生—心血管疾病]