刺槐素调节sestrin2/AMPK信号通路对心肌梗死大鼠心肌损伤的影响OA
Effect of Acacetin on myocardial damage in rats with myocardial infarction by regulating sestrin2/AMPK signaling pathway
目的:探究刺槐素调节应激诱导蛋白2(sestrin2)/腺苷酸活化蛋白激酶(AMPK)信号通路对心肌梗死(MI)大鼠心肌损伤的影响.方法:通过冠状动脉左前降支结扎法构建大鼠MI模型,将造模成功的75只大鼠随机分为模型(Model)组、低剂量刺槐素(L-刺槐素,12.5 mg/kg)组、中剂量刺槐素(M-刺槐素,25 mg/kg)组、高剂量刺槐素(H-刺槐素,50 mg/kg)组、高剂量刺槐素+sestrin2抑制剂(sh-sestrin2)(H-刺槐素+sh-sestrin2)组,每组15只,另外分别取15只大鼠作为对照(CK)组和假手术(Sham)组.超声心电图、TTC染色、HE染色、Masson染色、ELISA、Western blot分别检测大鼠心功能、MI面积、心肌组织病理损伤、心肌梗死周边纤维化、炎症因子及sestrin2/AMPK信号通路相关蛋白水平.结果:CK组和Sham组大鼠未发生MI,且心肌细胞排列规则,不存在炎症细胞浸润及胶原纤维沉积;与CK组比较,Sham组LVSP、LVEF、LVEDP、LVESV、IL-8、IL-1β、TNF-α、sestrin2、p-AMPK/AMPK蛋白表达差异均无统计学意义(P>0.05);Model组大鼠MI面积增加,心肌细胞排列紊乱,存在严重的炎症细胞浸润及胶原纤维沉积;Model组较Sham组LVSP、LVEF、sestrin2、p-AMPK/AMPK蛋白表达降低,LVEDP、LVESV、IL-8、IL-1β、TNF-α水平升高(P<0.05);与Model组比较,刺槐素各剂量组LVSP、LVEF、sestrin2、p-AMPK/AMPK蛋白表达升高,LVEDP、LVESV、MI面积、心肌组织病理损伤、胶原纤维沉积、IL-8、IL-1β、TNF-α水平降低(P<0.05);与H-刺槐素组比较,H-刺槐素+sh-sestrin2组LVSP、LVEF、sestrin2、p-AMPK/AMPK蛋白表达显著降低,LVEDP、LVESV、MI面积、心肌组织病理损伤、胶原纤维沉积、IL-8、IL-1β、TNF-α水平显著升高(P<0.05).结论:刺槐素对MI大鼠心肌损伤的改善可能与激活sestrin2/AMPK信号通路有关.
Objective:To investigate the effect of Acacetin on on myocardial damage in rats with myocardial infarction(MI)by regulating the stress-induced protein 2(sestrin2)/AMP-activated protein kinase(AMPK)signaling pathway.Methods:A MI rat model was constructed by left anterior descending coronary artery ligation method,75 successfully modeled rats were randomly assigned into Model group,low-dose Acacetin(L-Acacetin,12.5 mg/kg)group,medium-dose Acacetin(M-Acacetin,25 mg/kg)group,high-dose Acacetin(H-Acacetin,50 mg/kg)group,H-Acacetin+sestrin2 inhibitor(sh-sestrin2)group,with 15 rats in each group.Additionally,15 rats were selected respectively as control(CK)group and the Sham operation(Sham)group.Ultrasound elec-trocardiogram,TTC staining,HE staining,Masson staining,ELISA and Western blot were used to detect rat heart function,MI area,pathological damage of myocardial tissue,fibrosis around myocardial infarction,inflammatory factors,and levels of sestrin2/AMPK signaling pathway related proteins.Results:Rats in CK and Sham groups did not experience MI and had regular arrangement of myo-cardial cells,without inflammatory cell infiltration or collagen fiber deposition.Compared with CK group,there was no great difference in expressions of LVSP,LVEF,LVEDP,LVESV,IL-8,IL-1β,TNF-α,sestrin2 and p-AMPK/AMPK proteins in Sham group(P>0.05).MI area of rats in Model group was increased,arrangement of myocardial cells was disordered,and there was severe inflamma-tory cell infiltration and collagen fiber deposition.LVSP,LVEF,expressions of sestrin2 and p-AMPK/AMPK proteins were decreased in Model group compared to Sham group,while LVEDP,LVESV,levels of IL-8,IL-1β and TNF-α were increased(P<0.05).Com-pared with Model group,LVSP,LVEF,expressions of sestrin2 and p-AMPK/AMPK proteins were increased in each dose Acacetin groups,while LVEDP,LVESV,MI area,myocardial tissue patholo-gical damage,collagen fiber deposition,levels of IL-8,IL-1β and TNF-α were decreased(P<0.05).Compared with H-Acacetin group,LVSP,LVEF,expressions of sestrin2 and p-AMPK/AMPK proteins were greatly reduced in H-Acacetin+sh-sestrin2 group,while LVEDP,LVESV,MI area,myocardial tissue pathological dam-age,collagen fiber deposition,levels of IL-8,IL-1β and TNF-α were greatly increased(P<0.05).Conclusion:Improvement of Acac-etin on myocardial damage in MI rats may be related to the activation of sestrin2/AMPK signaling pathway.
熊俊锋;董婷;魏燕;代悉尼;蔡婉
湖北江汉油田总医院心内科,潜江 433100湖北江汉油田总医院骨科,潜江 433100湖北江汉油田总医院心内科,潜江 433100湖北江汉油田总医院心内科,潜江 433100上海中医药大学附属曙光医院心内科,上海 201203
医药卫生
刺槐素Sestrin2/AMPK信号通路心肌梗死心肌损伤
AcacetinSestrin2/AMPK signaling pathwayMyocardial infarctionMyocardial damage
《中国免疫学杂志》 2026 (8)
1847-1852,6
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