基于AMPK/SIRT1/PGC1α信号通路探究灯盏花素联合有氧运动对冠心病大鼠心功能障碍的改善作用及机制研究

关键词：灯盏花素  有氧运动  AMPK/SIRT1/PGC1α信号通路  冠心病

Keywords:breviscapine  aerobic exercise  AMPK/SIRT1/PGC1α signal pathway  coronary heart disease

摘要：

      摘要 目的：探究灯盏花素（BVP）联合有氧运动（AE）对冠心病大鼠心功能障碍的改善作用以及对AMPK/SIRT1/PGC1α信号通路的调节作用。 方法：将105只SD大鼠随机分为对照组、模型组、阳性组、BVP组、AE组、BVP+AE组、BVP+AE+AMPK抑制剂组（BVP+AE+BML-275组）。检测各组大鼠的心功能指标；检测各组大鼠的血脂水平；ELISA检测大鼠心肌组织炎症因子-C反应蛋白（CRP）、白细胞介素6（IL-6），肿瘤坏死因子-α（TNF-α）的含量；HE染色法观察心肌组织形态学特征；TUNEL法检测大鼠心肌细胞的凋亡情况；Western Blot检测大鼠心肌组织中AMPK/SIRT1/PGC-1α通路相关蛋白的表达。 结果：与对照组相比，模型组大鼠心功能指标LVEDV、LVESV、血脂指标TG、TC、LDL-C、CRP、IL-6、TNF-α的含量及细胞凋亡率升高，SV、LVEF、HDL-C含量以及p-AMPK、SIRT1和PGC-1α蛋白水平均降低（P<0.05）；与模型组相比，BVP组和AE组大鼠心功能指标LVEDV、LVESV、血脂指标TG、TC、LDL-C、CRP、IL-6、TNF-α的含量及细胞凋亡率降低，SV、LVEF、HDL-C含量以及p-AMPK、SIRT1和PGC-1α蛋白水平均升高（P<0.05）；与BVP组和AE组相比，阳性组和BVP+AE组大鼠的心功能指标LVEDV、LVESV、血脂指标TG、TC、LDL-C、CRP、IL-6、TNF-α的含量及细胞凋亡率降低，SV、LVEF、HDL-C含量以及p-AMPK、SIRT1和PGC-1α蛋白水平均升高（P<0.05）；AMPK抑制剂能够逆转BVP+AE联合对冠心病大鼠心脏损伤的缓解作用（P<0.05）。 结论：BVP联合AE能够通过激活AMPK/SIRT1/PGC1α信号通路来改善冠心病大鼠心功能障碍。

Abstract:

      Abstract Objective： To investigate the improvement effect of breviscapine （BVP） combined with aerobic exercise （AE） on cardiac dysfunction in rats with coronary heart disease and its regulatory effect on AMPK/SIRT1/PGC1α signaling pathway. Method： A total of 105 SD rats were randomly divided into control group， model group， positive group， BVP group， AE group， BVP+AE group， BVP+AE+AMPK inhibitor group （BVP+AE+BML-275 group）. The indexes of cardiac function were measured and the level of blood lipid of rats were detected. The contents of inflammatory factor C-reactive protein （CRP）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in myocardium of rats were detected by ELISA and the morphological characteristics of myocardium were observed by HE staining. The TUNEL method was used to detect the apoptosis of cardiomyocytes； and Western blot was used to detect the expression of AMPK/SIRT1/PGC-1α pathway related proteins in rat myocardium. Result： Compared with the control group， the LVEDV， LVESV， contents of TG， TC， LDL-C， CRP， IL-6， TNF-α， and the rate of apoptosis in the model group were higher， while the SV， LVEF， content of HDL-C， and the levels of p-AMPK， SIRT1 and PGC-1α protein were lower （P<0.05）. When compared with the model group, the LVEDV， LVESV， contents of TG， TC， LDL-C， CRP， IL-6， TNF-α， and the rate of apoptosis in BVP group and AE group were lower，while the SV， LVEF， content of HDL-C， and the levels of p-AMPK， SIRT1 and PGC-1α protein were higher （P<0.05）. When compared with the BVP group and AE group， the LVEDV， LVESV， contents of TG， TC， LDL-C， CRP， IL-6， TNF-α， and the rate of apoptosis in the positive group and BVP+AE group were lower，while the SV， LVEF， content of HDL-C， and the levels of p-AMPK， SIRT1 and PGC-1α protein were higher （P<0.05）. The AMPK inhibitor could reverse the relieving effect of BVP+AE combination on cardiac injury in rats with coronary heart disease （P<0.05）. Conclusion： BVP combined with AE can improve the cardiac dysfunction in rats with coronary heart disease by activating AMPK/SIRT1/PGC1α signal pathway.