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参附注射液辅助治疗对急性心肌梗死大鼠NOD样受体蛋白3/半胱氨酸天冬氨酸特异性蛋白酶1介导的细胞焦亡信号通路以及炎性因子水平的影响

Effect of adjuvant therapy of Shenfu Injection on NOD-like receptor protein 3/cysteine-aspartic acid-specific protease 1 mediated pyroptosis signaling pathway and inflammatory factor levels in rats with acute myocardial infarction

    摘要
  • 摘要:
    目的  探讨参附注射液辅助治疗对急性心肌梗死(AMI)大鼠NOD样受体蛋白3(NLRP3)/半胱氨酸天冬氨酸特异性蛋白酶1(Caspase-1)介导的细胞焦亡信号通路以及炎性因子水平的影响。
    方法  40只大鼠随机分为假手术组、模型组、倍他乐克组(0.9 mg/kg)和联合组(倍他乐克0.9 mg/kg联合参附注射液6 mL/kg), 每组10只, 连续灌胃3周。检测造模前、造模后和治疗3周时大鼠血清肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)、白细胞介素(IL)-6、IL-1β和肿瘤坏死因子-α(TNF-α)水平。造模后和治疗3周时，比较各组大鼠左心室射血分数(LVEF)、左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)等心脏彩超参数以及心肌梗死面积。应用实时荧光定量聚合酶链式反应(qRT-PCR)及Western blot检测心肌梗死面积NLRP3、Caspase-1的mRNA及其蛋白表达水平。
    结果  与假手术组相比，模型组造模后和治疗3周时cTnI、CK-MB、IL-6、IL-1β、TNF-α、心肌梗死面积、NLRP3 mRNA和Caspase-1 mRNA表达量均升高，差异有统计学意义(P < 0.05); 与模型组相比，倍他乐克组和联合组治疗3周时cTnI、CK-MB、IL-6、IL-1β、TNF-α、心肌梗死面积、NLRP3 mRNA和Caspase-1 mRNA表达量均降低，且联合组上述指标均低于倍他乐克组，差异有统计学意义(P < 0.05)。
    结论  参附注射液辅助治疗AMI能够进一步减轻心肌细胞损伤，缩小梗死面积，抑制炎症反应和细胞焦亡活性。

     

    Abstract:
    Objective  To investigate the effect of adjuvant therapy of Shenfu Injection on NOD-like receptor protein 3 (NLRP3)/cysteine-aspartic acid-specific protease 1 (Caspase-1) mediated pyroptosis signaling pathway and inflammatory factor levels in rats with acute myocardial infarction (AMI).
    Methods  A total of 40 rats were randomly divided into sham operation group, model group, betaloc group (0.9 mg/kg), and combination group (0.9 mg/kg betaloc combined with 6 mL/kg Shenfu Injection), with 10 rats in each group. The rats were treated by gavage continuously for 3 weeks. The levels of serum troponin I (cTnI), creatine kinase-MB (CK-MB), interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) in rats were detected before modeling, after modeling, and at 3 weeks of treatment. Echocardiographic parameters such as left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter(LVESD), left ventricular end-diastolic diameter (LVEDD), and myocardial infarction area were compared among groups after modeling and at 3 weeks of treatment. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of NLRP3 and Caspase-1 in the myocardium.
    Results  Compared with the sham operation group, the levels of cTnI, CK-MB, IL-6, IL-1β, TNF-α, myocardial infarction area, and the expressions of NLRP3 mRNA and Caspase-1 mRNA in the model group were significantly increased after modeling and at 3 weeks of treatment (P < 0.05); compared with the model group, the levels of cTnI, CK-MB, IL-6, IL-1β, TNF-α, myocardial infarction area, and the expressions of NLRP3 mRNA and Caspase-1 mRNA in the betaloc group and the combination group were significantly decreased at 3 weeks of treatment, and the above indicators in the combination group were significantly lower than those in the betaloc group (P < 0.05).
    Conclusion  Adjuvant therapy of Shenfu Injection for AMI can further alleviate myocardial cell injury, shorten infarction size, and inhibit inflammatory response and pyroptosis activity.

     

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