目的 探讨龙胆苦苷对心力衰竭大鼠心脏的改善作用及沉默信息调节因子2相关酶1（SIRT1）/腺苷酸活化蛋白激酶（AMPK）/过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1α）信号通路的影响。方法 构建心力衰竭模型大鼠并将其分模型组、卡托普利组、龙胆苦苷（50、100 mg/kg）组、龙胆苦苷＋SIRT1抑制剂（EX527）组，每组12只大鼠。另取12只健康大鼠作为对照组。测量各组大鼠心功能，ELISA试剂盒法检测各组大鼠血清中生长刺激表达基因2蛋白（ST-2）、N端前脑钠素（NT-proBNP）水平以及血清中氧化应激因子[超氧化物歧化酶（SOD）、丙二醛（MDA）]水平；HE染色法、Masson染色法检测心肌组织病理形态以及心肌组织中胶原纤维含量；透射电镜观察法检测各组大鼠心肌组织中线粒体形态；RT-qPCR法检测各组大鼠心肌组织中炎症因子表达水平；Western blotting法检测各组大鼠SIRT1、AMPK、PGC1α、III型胶原（Collagen III）、Ⅰ型胶原蛋白（Collagen I）和α-平滑肌肌动蛋白（α-SMA）蛋白含量。结果 与模型组相比，龙胆苦苷组大鼠心肌组织病损程度和心肌纤维化明显减轻，线粒体结构得到改善，心脏左室收缩末期内径（LVDs）和左室舒张末期内径（LVDd），血清中MDA、ST-2和NT‑proBNP水平，心肌组织胶原容积分数、白细胞介素（IL）-1β、IL-18和肿瘤坏死因子-α（TNF-α）mRNA表达水平以及Collagen III、Collagen I、α-SMA蛋白表达量明显降低，心脏左心室射血分数（LVEF）和左室短轴缩短率（FS）、血清中SOD水平以及心肌组织中SIRT1、p-AMPK/AMPK和PGC1α蛋白表达水平升高（P＜0.05）；与龙胆苦苷100 mg/kg组相比，龙胆苦苷＋EX527组大鼠心肌组织病损严重，线粒体肿胀破裂，心肌纤维化、炎性反应和氧化应激反应加剧、心功能下降，SIRT1、p-AMPK/AMPK和PGC1α蛋白表达量明显减少（P＜0.05）。结论 龙胆苦苷可能通过激活SIRT1/AMPK/PGC1α信号通路减轻心力衰竭大鼠心肌组织炎性反应和氧化应激损伤，从而发挥心保护功能。

Objective To investigate the improvement effect of gentiopicroside on the heart of rats with heart failure, and the impact on the SIRT1/AMPK/PGC1α signaling pathway. Methods Heart failure model rats were constructed, and divided into model group, aptopril group, gentiopicroside (50, 100 mg/kg) groups, and gentiopicroside＋SIRT1 inhibitor (EX527) group, with 12 rats in each group. Another 12 healthy rats were selected as the control group. The cardiac function of rats in each group was tested. The levels of ST-2 and NT-proBNP in the serum of rats in each group, and the levels of oxidative stress factors (SOD, MDA) in the serum were detected by ELISA kit method. The pathological morphology of myocardial tissue and the collagen fiber content in myocardial tissue were detected using HE staining and Masson staining methods. The mitochondrial morphology in the myocardial tissue of rats were observed by transmission electron microscopy. The levels of inflammatory factors in the myocardial tissue of rats in each group were detected by RT-qPCR method. The protein contents of SIRT1, AMPK, PGC1α, Collagen III, Collagen I, and α-SMA of rats in each group were detected by Western blotting. Results Compared with model group, the tissue damage status and myocardial fibrosis in rats in the gentiopicroside group were significantly reduced, the mitochondrial structure was improved, the heart LVDs and LVDd indicators, serum MDA, ST-2, and NT-proBNP levels, myocardial tissue collagen volume fraction, IL-1β, IL-18, and TNF-α mRNA expression levels, collagen III, collagen I and α-SMA protein expression levels were significantly lower, the heart LVEF and FS indicators, serum SOD level, and the SIRT1, p-AMPK/AMPK, and PGC1α protein expression levels in myocardial tissue were significantly higher (P＜0.05). Compared with gentiopicroside 100 mg/kg group, the gentiopicroside＋EX527 group showed severe damage, mitochondrial swelling and rupture, the myocardial fibrosis, inflammatory response, and oxidative stress response were exacerbated, the cardiac function decreased, the expression levels of SIRT1, p-AMPK/AMPK, and PGC1α proteins were significantly lower (P＜0.05). Conclusion Gentiopicroside may alleviate myocardial inflammatory response and oxidative stress injury in heart failure rats by activating the SIRT1/AMPK/PGC1α signaling pathway, thereby exerting cardiac protective function.

R285.5

内蒙古自治区自然科学基金面上基金项目（NJZZ21033）