天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (5): 473-478.doi: 10.11958/20190017

• 实验研究 • 上一篇    下一篇

机械加载可改善心肌梗死大鼠的心肌损伤

徐晋峰 1，李心乐 1，2，刘大全 1，2，张平 1，2△   

  1. 基金项目：天津滨海新区卫生计生委科技资助项目（2016BWKL002、2016BWKZ005） 作者单位：1天津医科大学基础医学院人体解剖与组织胚胎学系（邮编300070）；2北京协和医学院泰达国际心血管病医院再生医学中心 作者简介：徐晋峰（1992），男，硕士在读，主要从事机械加载与心血管疾病方面研究 △通讯作者 E-mail: pizhang2008@163.com
  • 收稿日期:2019-01-04 修回日期:2019-03-09 出版日期:2019-05-15 发布日期:2019-05-15
  • 通讯作者: 张平 E-mail:pizhang2008@163.com
  • 基金资助:
    国家自然科学基金面上项目;国家自然科学基金面上项目;国家自然科学基金面上项目;天津滨海新区卫生计生委科技资助项目;天津滨海新区卫生计生委科技资助项目

Mechanical loading can improve myocardial injury in myocardial infarction rats

XU Jin-feng1, LI Xin-le1,2, LIU Da-quan1,2, ZHANG Ping1,2△   

  1. 1 Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; 2 Centre for Regenerative Medicine, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College △Corresponding Author E-mail: pizhang2008@163.com
  • Received:2019-01-04 Revised:2019-03-09 Published:2019-05-15 Online:2019-05-15
  • Supported by:
    National Natural Science Foundation of China;National Natural Science Foundation of China;National Natural Science Foundation of China;Tianjin Binhai New Area Health and Family Planning Commission;Tianjin Binhai New Area Health and Family Planning Commission

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摘要： 摘要：目的 探讨机械加载对心肌梗死大鼠心肌损伤的改善作用。方法 选用8周龄Wistar雄性大鼠30只，体 质量约200 g，按随机数字表法分为假手术对照组（Sham组）、心肌梗死组（MI组）和心肌梗死机械加载治疗组（MI+L 组），每组10只，心肌梗死建模后1 d开始膝关节机械加载治疗2周。检测治疗后大鼠心电图Ⅱ导联ST段、心脏质量 指数（HMI）、左心室质量指数（LVMI）、心脏质量/胫骨长度，2，3，5－三苯基氯化四氮唑（TTC）染色检测左室舒张末内 径（LVEDD）和梗死范围；HE染色检测炎性细胞数；Masson染色检测胶原容积分数（CVF）；免疫组织化学染色检测核 因子（NF）-κB p65亚基、白细胞介素（IL）-6和基质金属蛋白酶（MMP）-9蛋白的表达。结果 与Sham组相比，心肌 梗死导致MI组心电图Ⅱ导联ST段抬高，HMI、LVMI、LVEDD、心脏质量/胫骨长度和梗死范围明显增加；机械加载治 疗后，MI+L组Ⅱ导联ST段抬高幅度下降，HMI、LVMI、LVEDD、心脏质量/胫骨长度和梗死范围较MI组明显降低（P＜ 0.05）。心脏组织学结果表明，心肌梗死导致炎性细胞数和CVF增加，通过加载治疗后，炎性细胞数和CVF明显改善 （P＜0.05）。免疫组化染色结果表明，心肌梗死导致大鼠心肌NF-κB p65、IL-6和MMP-9蛋白表达升高，机械加载能 够抑制3种蛋白的表达。相关性分析结果表明，NF-κB p65、IL-6和MMP-9三者之间表达呈正相关，三者与心室重构 指标（LVEDD、HMI、LVMI和心脏质量/胫骨长度）呈正相关。结论 机械加载可以明显改善心肌梗死大鼠心肌损伤， 该治疗作用可能与机械加载减轻心肌梗死后炎症反应和抑制心室重构有关。

关键词: 心肌梗死, 炎症, 心室重构, NF-κB, 基质金属蛋白酶9, 白细胞介素6, 大鼠, Wistar, 机械加载

Abstract: \Abstract: Objective To investigate the effects of mechanical loading on inflammation and ventricular remodeling in myocardial infarction (MI) rats. Methods Thirty male Wistar rats (8-week old, body weitht about 200 g) were randomly divided into sham operation group (Sham group), myocardial infarction model group (MI group) and mechanical loading treatment group (MI+L group) with 10 rats in each group. One day after the establishment of MI model in MI+L group, the knee loading was applied for 2 weeks. After mechanical loading, ST segment of the standard 12-lead electrocardiogram (ECG) lead Ⅱ, heart mass index (HMI), left ventricular mass index (LVMI) and heart weight/tibial length were measured. Left ventricular end-diastolic diameter (LVEDD) and infarct size were evaluated by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining. The number of infl ammatory cells was evaluated by HE staining. The collagen volume fraction (CVF) was evaluated by Masson staining. The protein expressions of nuclear factor- κb p65 (NF-κB p65), interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) were assessed by immunohistochemistry. Results Compared with Sham group, MI resulted in a significant increase in the lead Ⅱ ST-segment, HMI, LVMI, LVEDD, heart weight/tibial length and infarct size in MI group. After mechanical loading, there were significantly decrease in lead Ⅱ ST-segment, HMI, LVMI, LVEDD, heart weight/tibial length and infarct size in MI+L group than those in MI group (P＜0.05). Cardiac histology showed that MI caused inflammation and fibrosis in myocardial tissues. After loading therapy, the number of inflammatory cells and CVF were significantly improved (P＜0.05). Immunohistochemical analysis showed that MI resulted in the increased protein expressions of NF-κB p65, IL-6 and MMP-9. The mechanical loading obviously inhibited the expressions of NF-κB p65, IL-6 and MMP-9. There was a positive correlation between the expressions of NF-κB p65, IL-6 and MMP-9. There was a positive correlation between NF-κB p65, IL-6, MMP-9 and ventricular remodeling markers (LVEDD, HMI, LVMI and heart weight/tibial length). Conclusion Mechanical loading can significantly improve myocardial injury in MI rats, which may be related to alleviating inflammation and inhibiting ventricular remodeling after MI.

Key words: myocardial infarction, inflammation, ventricular remodeling, NF-kappa B, matrix metalloproteinase 9, interleukin-6, rats, Wistar, mechanical loading