我们的网站为什么显示成这样?

可能因为您的浏览器不支持样式,您可以更新您的浏览器到最新版本,以获取对此功能的支持,访问下面的网站,获取关于浏览器的信息:

|本期目录/Table of Contents|

替米沙坦、苯磺酸氨氯地平对大鼠心肌纤维化及血管紧张素-(1-7)的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第2期
页码:
165-168
栏目:
基础研究
出版日期:
2010-12-10

文章信息/Info

Title:
Effects of telmisartan and amlodipine on myocardial fibrosis and serum levels of angiotensin-(1-7) in hypertensive rats with abdominal aortic constriction
作者:
商卓1刘丽2王文3马丽媛3孟宪敏3
1.中国协和医科大学、中国医学科学院阜外医院心血管病科,北京 100037;2.秦皇岛市第一 医院心内科,河北 秦皇岛 066000;3.中国医学科学院阜外心血管病医院,北京 100037
Author(s):
SHANG Zhuo1 LIU Li2 WANG Wen3 MA Li-yuan3 MENG Xian-min3
1.Cardiovascular Institute & Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China; 2.Department of Cardiology, First Hospital of Qinhuangdao City, Qinhuangdao 066000, Hebei, China; 3.Cardiovascular Institute & Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
关键词:
替米沙坦苯磺酸氨氯地平心肌纤维化腹主动脉缩窄血管紧张素-(1-7)大鼠
Keywords:
myocardial fibrosis abdominal aortic constriction rat angiotensin-(1-7)
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的: 评价替米沙坦(TMST)、苯磺酸氨氯地平(ALDP)对腹主动脉缩窄(AAC)大鼠心肌纤维化的预防作用,了解其血清血管紧张素-(1-7)[Ang-(1-7)]水平的变化。方法: 32只8周龄雄性SD大鼠随机对24只施行AAC术,8只施行假手术。术后1周,将施行AAC术的24只大鼠随机分为TMST组[5 mg/(kg·d)]、ALDP组[5 mg/(kg·d)]和AAC对照组,每组8只(n=8)。给药8周后,采用ELISA方法,测定血清Ang-(1-7)的水平;用天狼猩红染色结合计算机图像分析心肌Ⅰ、Ⅲ型胶原,测定心肌胶原容积分数(collagen volume fraction,CVF)。结果: 与假手术组比较,在TMST组、ALDP组和AAC对照组中,心肌CVF、Ⅰ型胶原积分吸光度(integral optical density,IOD)值和Ⅰ/Ⅲ胶原比值明显增加(P<0.05),两种药物治疗组明显低于ACC对照组,TMST组明显低于ALDP组(P<0.05);Ⅲ型胶原IOD值也呈上升趋势,TMST组和ALDP组均明显低于ACC对照组(P<0.05);但两个药物组间没有明显差异。与AAC对照组比较,TMST组和ALDP组血清Ang(1-7)的水平均增加,但仅TMST组有显著差异(P<0.05)。心肌CVF、Ⅰ、Ⅲ型胶原IOD值及Ⅰ/Ⅲ胶原比值与血清Ang-(1-7)的水平均呈负相关(P<0.05),相关系数r分别为-0.47(P<0.05)、-0.38(P<0.05)、-0.32(P<0.05)和-0.41(P<0.05)。结论: TMST和ALDP均能较好地预防AAC大鼠心肌纤维化,TMST的作用似优于ALDP。Ang-(1-7)可能参与了TMST抑制心肌纤维化的过程。
Abstract:
AIM: To evaluate the preventive effects of telmisartan (TMST) and amlodipine (ALDP) on myocardial fibrosis in hypertensive rats with abdominal aortic constriction (AAC) and to observe the changes of angiotensin-(1-7) [Ang-(1-7)] levels. METHODS: AAC (n=24) and sham operation (n=8) were performed on 8-week-old male Sprague Dawley rats. After 1 week of operation, AAC rats were randomly divided into three groups: TMST (n=8), ALDP (n=8) and AAC control (n=8), respectively. The first two groups were treated by TLST and ALDP at doses of 5 mg/(kg·day), respectively. After 8 weeks, serum levels of Ang-(1-7) were determined by ELISA and myocardial collagen volume fraction (CVF), collagen type I, type III and I/III were assessed by sirius red staining combined with computer image analysis. RESULTS: Compared with those in sham group, the myocardial CVF, integral optical density (IOD) values of collagen type I and I/III increased in TLST group, ALDP group and AAC control group (P<0.05), with the parameters in treatment groups significantly lower than those in AAC control group, and the parameters in TMST group significantly lower than those in ALDP group. IOD values of collagen type III also were on the rise, with the values in treatment groups significantly lower than those in AAC control group, but there were no significant difference between TMST group and ALDP group. Compared with AAC control group, TMST and ALDP both increased serum levels of Ang-(1-7), but only the increase in TMST group was significant (P<0.05). However, no significant difference was observed between the two groups. Relationships between serum levels of Ang-(1-7) and myocardial CVF, IOD values of collagen type I and type III, I/III were negatively correlated (P<0.05), and r value was -0.47 (P<0.05), -0.38 (P<0.05), -0.32 (P<0.05)and -0.41 (P<0.05), respectively. CONCLUSION: Both TMST and ALDP prevent myocardial fibrosis in hypertensive rats with AAC but TMST seems to be more effective. Ang-(1-7) may be involved in the process of inhibiting myocardial fibrosis with TMST.

参考文献/References

[1]刘丽,王文,孟宪敏,等. 高血压大鼠左室肥厚差异蛋白质组学研究[J]. 中华高血压杂志, 2008, 16(6):516-522.

[2]Rodriguez-Iturbe B, Quiroz Y, Kim CH, et al. Hypertension induced by aortic coarctation above the renal arteries is associated with immune cell infiltration of the kidneys[J]. Am J Hypertens, 2005, 18(11):1449-1456.

[3]张晶,何静雯,王泰龄,等. 苦叶酸天狼猩红偏振光法鉴别Ⅰ型及Ⅲ型胶原纤维[J]. 中华病理会学杂志, 1996, 25(3):180-181.

[4]Weber KT, Brilla CG, Janicki JS. Myocardial fibrosis: functional significance and regulatory factors[J]. Cardiovasc Res, 1993, 27(3):341-348.

[5]Burnier M. Telmisartan: a different angiotensin II receptor blocker protecting a different population?[J]. J Int Med Res, 2009, 37(6):1662-1679.

[6]Taal MW, Brenner BM. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists[J]. Kidney Int, 2000, 57(5):1803-1817.

[7]Liang B, Leenen FH. Prevention of salt-induced hypertension and fibrosis by AT1-receptor blockers in Dahl S rats[J]. J Cardiovasc Pharmacol, 2008, 51(5):457-466.

[8]Lu JC, Cui W, Zhang HL, et al. Additive beneficial effects of amlodipine and atorvastatin in reversing advanced cardiac hypertrophy in elderly spontaneously hypertensive rats[J]. Clin Exp Pharmacol Physiol, 2009, 36(11):1110-1119.

[9]Epstein M. Lercanidipine: a novel dihydropyridine calcium-channel blocker[J]. Heart Dis, 2001, 3(6):398-407.

[10]Iwata M, Cowling RT, Gurantz D, et al. Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects[J]. Am J Physiol Heart Circ Physiol, 2005, 289(6):H2356-H2363.

[11]Santos RA, Ferreira AJ, Simes E, et al. Recent advances in the angiotensin-converting enzyme 2-angiotensin(1-7)-Mas axis[J]. Exp Physiol, 2008, 93(5):519-527.

[12]Zhang C, Knudson JD, Setty S, et al. Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors[J]. Am J Physiol Heart Circ Physiol, 2005, 288(5):H2154-H2162.

[13]王立军,马虹,廖新学,等. 血管紧张素转换酶-2在压力超负荷大鼠心肌中的表达及替米沙坦干预的实验研究[J]. 中国危重病急救医学, 2008, 20(4):218-222.

[14]Huentelman MJ, Grobe JL, Vazquez J, et al. Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats[J]. Exp Physiol, 2005, 90(5):783-790.

[15]Ferreira AJ, Santos RA. Cardiovascular actions of angiotensin-(1-7)[J]. Braz J Med Biol Res, 2005, 38(4):499-507.

备注/Memo

备注/Memo:
收稿日期:2010-05-04.通讯作者:王文,教授,主要从事高血压发病机制和防治研究mail:wangfw@yahoo.cn 作者简介:商卓,主治医师,博士生Email:zhuoshang@hotmail.com
更新日期/Last Update: 2010-12-10