目的 探討龍膽苦苷對心力衰竭大鼠心臟的改善作用及沉默信息調節(jié)因子2相關酶1（SIRT1）/腺苷酸活化蛋白激酶（AMPK）/過氧化物酶體增殖物激活受體γ共激活因子1α（PGC1α）信號通路的影響。方法 構建心力衰竭模型大鼠并將其分模型組、卡托普利組、龍膽苦苷（50、100 mg/kg）組、龍膽苦苷＋SIRT1抑制劑（EX527）組，每組12只大鼠。另取12只健康大鼠作為對照組。測量各組大鼠心功能，ELISA試劑盒法檢測各組大鼠血清中生長刺激表達基因2蛋白（ST-2）、N端前腦鈉素（NT-proBNP）水平以及血清中氧化應激因子[超氧化物歧化酶（SOD）、丙二醛（MDA）]水平；HE染色法、Masson染色法檢測心肌組織病理形態(tài)以及心肌組織中膠原纖維含量；透射電鏡觀察法檢測各組大鼠心肌組織中線粒體形態(tài)；RT-qPCR法檢測各組大鼠心肌組織中炎癥因子表達水平；Western blotting法檢測各組大鼠SIRT1、AMPK、PGC1α、III型膠原（Collagen III）、Ⅰ型膠原蛋白（Collagen I）和α-平滑肌肌動蛋白（α-SMA）蛋白含量。結果 與模型組相比，龍膽苦苷組大鼠心肌組織病損程度和心肌纖維化明顯減輕，線粒體結構得到改善，心臟左室收縮末期內徑（LVDs）和左室舒張末期內徑（LVDd），血清中MDA、ST-2和NT‑proBNP水平，心肌組織膠原容積分數(shù)、白細胞介素（IL）-1β、IL-18和腫瘤壞死因子-α（TNF-α）mRNA表達水平以及Collagen III、Collagen I、α-SMA蛋白表達量明顯降低，心臟左心室射血分數(shù)（LVEF）和左室短軸縮短率（FS）、血清中SOD水平以及心肌組織中SIRT1、p-AMPK/AMPK和PGC1α蛋白表達水平升高（P＜0.05）；與龍膽苦苷100 mg/kg組相比，龍膽苦苷＋EX527組大鼠心肌組織病損嚴重，線粒體腫脹破裂，心肌纖維化、炎性反應和氧化應激反應加劇、心功能下降，SIRT1、p-AMPK/AMPK和PGC1α蛋白表達量明顯減少（P＜0.05）。結論 龍膽苦苷可能通過激活SIRT1/AMPK/PGC1α信號通路減輕心力衰竭大鼠心肌組織炎性反應和氧化應激損傷，從而發(fā)揮心保護功能。

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

內蒙古自治區(qū)自然科學基金面上基金項目（NJZZ21033）