天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (8): 800-804.doi: 10.11958/20190410

• 实验研究 • 上一篇    下一篇

PKD1/HDAC5轴在心肌梗死大鼠损伤心肌组织修复中的作用

杨雷，刘萍，刘暖，陶玲玲，毛秉豫△   

  1. 南阳理工学院河南省张仲景方药与免疫调节重点实验室（邮编473004）
  • 收稿日期:2019-02-15 修回日期:2019-06-03 出版日期:2019-08-15 发布日期:2019-08-16
  • 通讯作者: 杨雷 E-mail:tonyraly@126.com
  • 作者简介:杨雷（1977），男，博士，副教授，主要从事中西医结合抗心血管疾病发病机制研究
  • 基金资助:
    黄芪丹参提取物配伍调控蛋白激酶D1抑制病理性心肌肥大和促血管新生治疗心肌梗死的作用机制研究

The role of PKD1/HDAC5 axis on myocardial repair in rats with myocardial infarction

YANG Lei, LIU Ping, LIU Nuan, TAO Ling-ling, MAO Bing-yu△   

  1. Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation,Nanyang Institute of Technology, Nanyang 473004, China
  • Received:2019-02-15 Revised:2019-06-03 Published:2019-08-15 Online:2019-08-16

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摘要： 摘要：目的 分析蛋白激酶D1（PKD1）/Ⅱa类组蛋白去乙酰化酶5（HDAC5）轴对受损心肌梗死大鼠心肌修复的 影响。方法 根据随机数字表法把40只Wistar大鼠划分为4组：假手术组、模型组、PKD1（2 mg·kg-1·d-1 PKD1）用药组和阻断剂CID755673（2 mg·kg-1·d-1 PKD1+10 ng·kg-1·d-1 CID755673）组，每组10只。模型组采用经典的左冠状动脉结扎术复制心肌梗死模型，假手术组开胸手术但没有进行结扎处理。模型组和假手术对照组均给予治疗组相同剂量的生理盐水。采用间隔1日1次的尾静脉注射方式给药，共28 d。采用HE染色分析心肌组织病理变化，Masson染色分析心肌组织的胶原变化，TUNEL法检测心肌细胞的凋亡程度，免疫印迹法和免疫组化染色检测心肌细胞HDAC5、肌细胞增强因子2（MEF2）和心肌肌钙蛋白I（cTn I）的表达。结果 心肌组织病理变化表明，假手术组大鼠心肌组织正常，无坏死和炎症浸润，胶原占比很低，偶见凋亡的心肌细胞，HDAC5和MEF2阳性细胞数量较少，cTn I阳性细胞数量较多；和假手术组相比，模型组大鼠心肌组织坏死明显，伴炎症浸润，胶原占比、凋亡的心肌细胞数量和MEF2阳性细胞数量均显著增加（P＜0.05），cTn I阳性细胞数量显著减少（P＜0.05）。和模型组相比，PKD1治疗能显著改善心肌梗死大鼠心肌坏死程度，使受损心肌组织胶原占比、凋亡的心肌细胞数量和MEF2阳性细胞数量均显著减少（P＜0.05），cTn I阳性细胞数量显著升高（P＜0.05）；而CID755673可以阻断PKD1的这一治疗作用。结论 PKD1可能具有结合HDAC5促心肌梗死大鼠损伤心肌组织修复的作用，这一作用能够被CID755673所阻断。

关键词: 心肌梗死, 蛋白激酶类, 组蛋白脱乙酰基酶类, 肌钙蛋白I, 细胞凋亡, 肌细胞增强因子2

Abstract: Abstract: Objective To analyze the effect of PKD1/HDAC5 axis on myocardial repairment in rats with myocardial infarction. Methods Forty male Wistar rats were divided into four groups: sham-operated (Sham) group, model group,PKD1 treatment group (2 mg·kg-1 ·d-1 PKD1) and CID755673 blocker group (2 mg·kg-1 ·d-1 PKD1+10 ng·kg-1 ·d-1 CID755673) according to the rule of random number table. The model group was treated with classical left coronary artery ligation to reproduce the myocardial infarction model, while the sham-operated group underwent thoracotomy without ligation. An equal amount of normal saline was injected in the model group and sham group. All administrations were performed via a tail vein injection every other day for 28 days. The pathological changes of myocardium were analyzed by HE staining, the changes of collagen in myocardial tissue were analyzed by Masson staining, the apoptotic changes of cardiomyocytes were detected by TUNEL method, and the immunohistochemistry and immunoblotting were used to detect the expressions of HDAC5, myocyte enhancer factor 2 (MEF2) and cardiac troponin I (cTn I). Results The pathological results showed that the rat myocardium was normal in the Sham group, no necrosis and inflammatory infiltration, low percentage of collagen, occasional apoptotic myocardial cells, fewer HDAC5 and MEF2 positive cells and a large number of cTn I positive cells. Compared with the Sham group, there were obvious myocardial necrosis, inflammatory infiltration, higher percentage of collagen, apoptotic myocardium and MEF2 positive cells, and less cTn I positive cells in the model group (P＜0.05). Compared with the model group, PKD1 treatment could significantly improve the degree of myocardial necrosis in rats with myocardial infarction, and significantly reduce the proportion of collagen in damaged myocardial tissues, decrease the number of apoptotic myocardial cells and MF2-positive cells (P＜0.05), and increase the number of cTn I-positive cells (P＜0.05), while CID755673 could block the therapeutic effect of PKD1. Conclusion PKD1 combined with HDAC5 might promote myocardial tissue in rats with myocardial infarction, which could be blocked by CID755673.

Key words: myocardial infarction, protein kinases, histone deacetylases, troponin I, apoptosis, myocyte enhancer2