机械加载可改善心肌梗死大鼠的心肌损伤

Mechanical loading can improve myocardial injury in myocardial infarction rats

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200g,按随机数字表法分为假手术对照组(Sham组)、心肌梗死组(M I组)和心肌梗死机械加载治疗组(M I+L组),每组10只,心肌梗死建模后1d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(H MI)、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(N F)-κBp65亚基、白细胞介素(IL)-6和基质金属蛋白酶(M MP)-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-κBp65、 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-κBp65、 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。

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 inflammatory 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.