中国药物警戒 ›› 2017, Vol. 14 ›› Issue (7): 385-388.

• 基础与临床研究 •    下一篇

培哚普利对大鼠心梗后早期心室重构心肌胶原蛋白的影响

耿涛1, 刘剑刚2, 张蕾2*   

  1. 1 中国中医科学院广安门医院,北京 100053;
    2 中国中医科学院西苑医院,北京 100091
  • 收稿日期:2017-08-16 修回日期:2017-08-16 出版日期:2017-07-20 发布日期:2017-08-16
  • 通讯作者: 张蕾,女,博士,主治医师,心血管病研究。E-mail:13581684969@163.com
  • 作者简介:耿涛,男,博士,主治医师,心血管病研究。
  • 基金资助:
    国家自然科学基金（81173384）：Walker 256肿瘤心梗大鼠同体模型血管新生及赤芍组分干预的分子机制

Protective Effect of Perindopril on Myocardium Collagen During the Early Phase of Ventricular Remodeling after Myocardial Infarction of Rats

GENG Tao1, LIU Jian-gang2, ZHANG Lei2,*   

  1. 1 Guang'anmen Hospital, China Academy of Chinese Medical Sciences,Beijing 100053, China;
    2 Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
  • Received:2017-08-16 Revised:2017-08-16 Online:2017-07-20 Published:2017-08-16

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摘要： 目的 观察培哚普利对急性心梗（acute myocardial infarction,AMI）大鼠早期心室重构（ventricular remodeling,VR）缺血的心肌胶原蛋白的影响。方法 60只Wistar大鼠随机分为以下4组：空白组、假手术组、模型组、培哚普利组（0.36 mg·kg-1）。通过结扎大鼠冠状动脉前降支制作AMI模型,假手术组仅穿线不结扎。造模成功后的第2天开始灌胃给药,1次/天,连续4周,除培哚普利组外均给予等量生理盐水。4周后麻醉取材检测左室重量指数（left ventricular mass index, LVMI）,HE染色观察心肌病理,放免法检测Ⅲ型前胶原、Ⅳ型胶原在血清中的含量,免疫组化法检测缺血心肌组织中Ⅰ、Ⅲ型胶原蛋白的表达情况。结果 与假手术组比较,造模4周后模型组大鼠心肌左室重量和LVMI显著增加,缺血心肌Ⅰ、Ⅲ型胶原、Ⅲ型前胶原蛋白表达显著增加（P <0.01）。与模型组比较,培哚普利能明显降低心脏LVMI,由3.32 mg·g-1下降到2.55 mg·g-1,下降了23.2%,心肌Ⅲ型前胶原含量由55.96 μg·L-1下降到45.61 μg·L-1,且对Ⅰ、Ⅲ型胶原蛋白的含量有显著抑制作用（P <0.05,P <0.01）。结论 培哚普利能降低大鼠LVMI、Ⅲ型前胶原含量,抑制AMI后早期缺血心肌Ⅰ、Ⅲ型胶原蛋白的表达,对心梗后缺血心肌有保护作用,是抑制AMI后早期VR的机制之一。

关键词: 培哚普利, 急性心肌梗死, 心室重构, 胶原蛋白, 大鼠

Abstract: Objective To investigate the protective effect of perindopril on myocardium collagen during the early phase of ventricular remodeling (VR) after myocardial infarction of rats. Methods 60 Wistar rats were divided into 4 groups randomly: which were blank group, sham operation group, model group and perindopril group. The model was established through ligating the left anterior descending coronary of rats. Meanwhile, suture was penetrated around the left anterior but not tied in sham operation group. Intragastrical administration started from the next day after model establishment, once a day for 4 weeks. The dosage of intragastrical administration in perindopril group was 0.36 mg·kg-1, the other groups were given intragastric administration with equivalent distilled water. After 4 weeks, left ventricular mass index(LVMI) was tested, myocardium pathology was made by hematoxylin and eosin stain, the content of precollagen Ⅲ and collagen Ⅳ in serum were tested by radio-immunity method, expression of collagenⅠand Ⅲ in ischemic myocardium were tested by immunohistochemical method. Results Compared with sham operation group, left ventricular mass and LVMI in model group increased significantly, the expression of collagenⅠ and collagen Ⅲ and precollagen Ⅲ increased significantly(P <0.01). Compared with model group, the LVMI decreased significantly from 3.32 mg·g-1 to 2.55 mg·g-1 and content of precollagen Ⅲ decreased from 55.96 μg·L-1 to 45.61 μg·L-1 in perindopril group. Moreover, the expression of collagenⅠ and collagen Ⅲ were inhibited in perindopril group(P<0.05, P <0.01). Conclusion Perindopril can play the role of protecting ischemic myocardium and inhibiting VR after AMI by decreasing the LVMI and content of precollagen Ⅲ, inhibiting the expression of collagenⅠ and collagen Ⅲ in rats.

Key words: perindopril, acute myocardial infarction, ventricular remodeling, collagen, rat

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