摘要
目的探讨黄芪生脉饮(HSY)调控嘌呤能受体P2X配体门控离子通道7(P2X7R)/NOD样受体蛋白家族含pyrin结构域3(NLRP3)通路对急性心肌梗死(AMI)大鼠心肌纤维化的影响。方法60只大鼠分为假手术组和模型组各10只。结扎左前降支构建AMI大鼠模型,随机分为AMI组、HSY-低(灌胃1.6 ml/kg HSY)组、HSY-高组(灌胃6.2 ml/kg HSY)、复方丹参组(灌胃300 mg/kg复方丹参)和HSY-高+P2X7R激动剂-ATP组(灌胃6.2 ml/kg HSY,尾静脉注射10 mmol/L ATP)。干预结束后,检测心功能、心肌损伤及炎性因子标志物;制备组织切片,检测病理损伤、心肌纤维化情况以及Ⅰ、Ⅲ型胶原(COL1A1、COL3A1)。Western blotting检测P2X7R、NLRP3、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、活化的Caspase-1蛋白表达。结果与假手术组相比,AMI组舒张末期内径(LVEDD)、脑利钠肽(BNP)、心肌肌钙蛋白Ⅰ(cTnⅠ)、纤维化体积分数升高,COL1A1、COL3A1阳性表达,TNF-α、IL-1β、P2X7R、NLRP3及活化的Caspase-1蛋白表达增加(P<0.05),射血分数(LVEF)降低(P<0.05);与AMI组相比,HSY-低、HSY-高组、复方丹参组LVEDD、BNP、cTnⅠ、纤维化体积分数降低,COL1A1、COL3A1阳性表达、TNF-α、IL-1β、P2X7R、NLRP3及活化的Caspase-1蛋白表达减少(P<0.05),但LVEF增加(P<0.05);与HSY-高组相比,HSY-高+ATP组LVEDD、BNP、cTnⅠ、纤维化体积分数升高,COL1A1、COL3A1阳性表达、TNF-α、IL-1β、P2X7R、NLRP3及活化的Caspase-1蛋白表达增加(P<0.05),但LVEF降低(P<0.05)。结论HSY通过抑制P2X7R/NLRP3通路减轻AMI大鼠心肌纤维化。
Objective To investigate the effect of Huangqi Shengmai Yin(HSY)on myocardial fibrosis in rats with acute myocardial infarction(AMI)by adjusting P2X purinoceptor 7(P2X7R)/NOD-like receptor protein 3(NLRP3)pathway.Methods Sixty rats were divied into a sham operation group and model group(5 groups),with 10 rats in each group.The AMI rat model was constructed by ligating the left anterior descending branch and randomly grouped into AMI group,the HSY-low group(intragastric administration of 1.6 ml/kg HSY),the HSY group(intragastric administration of 6.2 ml/kg HSY),the compound miltiorhiza group(intragastric administration of 300 mg/kg),and the HSY-high+P2X7R agonist-ATP group(intragastric administration of 6.2 ml/kg HSY,and tail vein administration of 10 mmol/L ATP).After the intervention,cardiac function,myocardial injury and inflammatory factor markers were detected.The tissue sections were prepared to examine pathological changes,myocardial fibrosis,type I and type II collagen(COLIAl,COL3A1).Western blotting was performed to detecte the protein expression of P2X7R,NLRP3,tumor necrosis factor-α(TNF-α),interleukin-1p(IL-1β),and the expression of activated Caspase-1.Results Compared with the sham surgery group,the AMI group showed an increase in the left ventricular end diastolic diameter(LVEDD),the coatent of brain natriuretic peptide(BNP)and cardiac troponin I(cTn I),fibrosis volume fraction,the positive expression of COLIA1,COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P<0.05),and a decrease in left ventricular ejection fraction(LVEF)(P<0.05).The HSY-low group,HSY-high groups,and compound miltiorhiza group showed a decrease in LVEDD,the content of BNP and cTn I,fibrosis volume fraction,the positive expression of COL1A1 and COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P<0.05),and an increase in LVEF than these in the AMI group(P<0.05).The HSY-high+ATP group showed an increase in LVEDD,the content of BNP,cTn I,fibrosis volume fraction,the positive expression of COLIA1 and COL3Al,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P<0.05),and a decrease in LVEF than those in the HSY-high group(P<0.05).Conclusion HSY inhibits P2X7R/NLRP3 pathway to alleviate myocardial fibrosis in AMI rats.
作者
马艺杰
张由建
王记培
李丹丹
靳津鸽
MA Yijie;ZHANG You-jian;WANG Ji-pei;LI Dan-dan;JIN Jin-ge(Department of Cardiovascular Medicine,Henan Provincial Chest Hospital,Zhengzhou 450008,China)
出处
《解剖学报》
2025年第6期713-720,共8页
Acta Anatomica Sinica
