Gαq/11信号转导通路在血管紧张素Ⅱ引起心肌肥大中的作用  

Effect of Gαq/11-mediated signal transduction pathway in cardiac hypertrophy induced by angiotensin II

作　　者：白桦[1] 邢东琦[2] 孙银平[3] 吴立玲[2] 

机构地区：[1]邮电总医院心内科,北京100032 [2]北京大学医学部生理与病理生理学系,北京100083 [3]新乡医学院病理生理教研室,河南新乡453003

出　　处：《中国病理生理杂志》2002年第1期8-12,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目 (No .39870 35 6 )

摘　　要：目的 :研究Gαq/ 11介导的信号转导通路在血管紧张素II(AngII)引起心肌肥大中的作用。方法 :复制2K1C肾性高血压大鼠模型 ,分别在术后 1、2、4、8周观察高血压大鼠和卡托普利治疗后大鼠血流动力学的变化 ;测定心肌肥大指数并用放免法测定心脏AngII含量 ;采用免疫印迹法测定心脏Gαq/ 11含量 ;以 [3 H]标记的 4,5 -二磷酸磷脂酰肌醇 (PIP2 )为底物 ,测定磷脂酶C(PLC)活性。培养乳鼠心肌细胞 ,测定AngII刺激后心肌细胞 [3 H]-亮氨酸掺入和Gαq/ 11含量的变化。结果 :2K1C大鼠在术后 2周血压开始明显升高并从 2周开始出现心肌肥大 ;心脏AngII含量在术后 1- 8周均明显增高 ;心脏Gαq/ 11含量在 4周和 8周时分别比假手术组高 2 5 .0 %和 35 8% (P <0 0 5 )。PLC活性在 2周、4周和 8周时比假手术组分别高 12 8%、2 1 8%和 2 1 0 % (P <0 0 5 )。卡托普利治疗可以降低血压逆转心肌肥大 ,并抑制Gαq/ 11含量增加和PLC活化。AngII刺激培养的心肌细胞 1h即可引起Gαq/ 11含量增加 ,刺激2 4h[3 H]-亮氨酸掺入才明显增加。结论 :激活Gαq/ 11及其下游的信号分子是介导AngII引起心肌肥大的重要信号转导途径。AIM: To investigate the role of Gαq/11-mediated signal transduction pathway in cardiac hypertrophy induced by angiotensin II (AngII). METHODS: Renal hypertension was performed by placing a sliver clip around the left renal artery(2K1C). Hemodynamic parameters, the ratio of left ventricular weight to body weight, the AngII contents and the activities of phospholipase C (PLC) in myocardium were measured at 1st, 2nd, 4th and 8th week after operation, respectively. The levels of Gαq/11 were assayed by Western blot analysis. -leucine incorporation and levels of Gαq/11 were measured in cultured neonatal rats ventricular myocyte after AngII stimulation. RESULTS: In 2K1C group, blood pressure and the ratio of left ventricle of heart to body weight were significantly increased compared with sham group between 2nd to 8th week. AngII content increased from 1st to 8th week after operation. Compared with the sham group, levels of Gαq/11 in 2K1C group increased by 25.0% and 35.8% at 4th and 8th week( P< 0 05), respectively. PLC activities of 2K1C group were significantly increased at 2nd, 4th, and 8th week ( P< 0 05). Gαq/11 protein levels was upregulated in myocyte stimulated by AngII and this effect presented before the increasing of -leucine incorporation. CONCLUSION: Activation of the Gαq/11-mediated signal transduction pathway plays an important role in cardiac hypertrophy induced by AngII.

关 键 词：肾性高血压 心肌肥大 血管紧张素Ⅱ 心力衰竭 

分 类 号：R542.2[医药卫生—心血管疾病]