[肾素-血管紧张素-醛固酮系统拮抗剂对自发性高血压大鼠心肌缝隙连接蛋白43表达的影响]

[Effect of RAAS antagonist on the expression of gap junction cx43 in myocardium of spontaneously hypertensive rat].

作者信息

Tan Li-Li, Li Lu, Liu Li-Min, Zhao Hong-Li

机构信息

First Department of Cardiology, Shenzhou Hospital Affiliated to Shenyang Medical College, Shenyang 110002, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2013 Jul;44(4):531-5, 549.

PMID:24059102

Abstract

UNLABELLED

OBJECTIVE To investigate the expression of gap junction protein Cx43 in the cardiac muscle of spontaneous hypertensive rat and the effects of various antagonists against renin angiotensin aldosterone system (RAAS) on Cx43 expression. METHODS 70 spontaneous hypertensive rats of 8-week age, 200-gram weight were separated into 7 groups, as hypertension, ramipril, telmisartan, eplerenone, ramipril + telmisartan, telmisartan + eplerenone, and ramipril+eplerenone treatment group. Another 10 healthy Wistar rats of the same age and weight were used as control group. All the rats were given intragastric administration at 8 a. m. every morning, and measured arteria caudilis pressure at 0, 4 and 8 week, respectively. 8 weeks later, all the rats were sacrificed, and the hearts were taken to measure the weight of left ventricle and the ratio of left ventricle to body weight. Myocardial fibrosis was observed by H&E staining of paraffin embedded sections, and Cx43 expression was examined by RT-PCR and western blot.

RESULTS

The arteria caudilis pressure of spontaneous hypertensive rats was significantly higher than that of healthy control Wistar rats (P < 0.01). The decreased blood pressure was observed in RAAS antagonists treated rats, compared with hypertension group (P < 0.05). The combined treatment of telmisartan and eplerenone had the best effect of lowering blood pressure. Moreover, the weight of left ventricle, the ratio of left ventricle to body weight, myocardial fibrosis and angiotensin 11 were all prominently decreased in telmisartan and eplerenone combination group (P < 0.01). The expression of Cx43 in spontaneous hypertensive rats was significantly lower than that of healthy control Wistar rats (P < 0.01). Increased Cx43 expression was observed in RAAS antagonists treated rats, compared with hypertension group (P < 0.05).

CONCLUSION

The expression of gap junction protein Cx43 was significantly down-regulated in spontaneous hypertensive rats, while RAAS antagonists increased Cx43 expression. The combination of telmisartan and eplerenone effectively recovered the expression of Cx43 and probably reversed hypertension.

摘要

未标记

目的研究缝隙连接蛋白Cx43在自发性高血压大鼠心肌中的表达以及各种肾素-血管紧张素-醛固酮系统（RAAS）拮抗剂对Cx43表达的影响。方法将70只8周龄、体重200克的自发性高血压大鼠分为7组，即高血压组、雷米普利组、替米沙坦组、依普利酮组、雷米普利+替米沙坦组、替米沙坦+依普利酮组和雷米普利+依普利酮治疗组。另取10只同年龄、体重的健康Wistar大鼠作为对照组。所有大鼠每天上午8点进行灌胃给药，分别在0、4和8周测量尾动脉血压。8周后，处死所有大鼠，取出心脏测量左心室重量及左心室与体重之比。通过石蜡包埋切片的苏木精-伊红（H&E）染色观察心肌纤维化情况，并通过逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测Cx43表达。

结果

自发性高血压大鼠的尾动脉血压显著高于健康对照Wistar大鼠（P<0.01）。与高血压组相比，RAAS拮抗剂治疗的大鼠血压降低（P<0.05）。替米沙坦和依普利酮联合治疗降压效果最佳。此外，替米沙坦和依普利酮联合组的左心室重量、左心室与体重之比、心肌纤维化和血管紧张素Ⅱ均显著降低（P<0.01）。自发性高血压大鼠中Cx43的表达显著低于健康对照Wistar大鼠（P<0.01）。与高血压组相比，RAAS拮抗剂治疗的大鼠Cx43表达增加（P<0.05）。