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

商卓; 刘丽; 王文; 马丽媛; 孟宪敏

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

Effects of telmisartan and amlodipine on myocardial fibrosis and serum levels of angiotensin-(1-7) in hypertensive rats with abdominal aortic constriction

摘要

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.

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