目的 探索芪参益气滴丸（QSYQ）通过MST/Hippo信号通路对小鼠心肌缺血再灌注损伤（MIRI）后炎症反应的影响。方法 将60只C57BL/6J小鼠按随机数字表法分为6组：假手术组、模型组、XMU-MP-1（选择性抑制Hippo信号通路中的MST靶点，l mg·kg^-1）组和QSYQ低、中、高剂量（5.85、11.70、23.40 g·kg^-1）组，每组15只。造模前QSYQ组小鼠ig予以QSYQ（用蒸馏水配制成混悬液）4周，20 mL·kg^-1，每天给药1次，XMU-MP-1组腹膜内注射XMU-MP-1，每隔1 d给药1次，连续给药4周，假手术组和模型组ig给予等量0.9%氯化钠溶液。除假手术组外，采用左冠状动脉前降支结扎术制备小鼠MIRI模型，缺血30 min复灌2 h后取材。利用TTC染色评估心肌梗死面积百分比，HE染色观察心脏组织病理改变，TUNEL染色评估心肌细胞凋亡情况，ELISA试剂盒检测血清炎症因子白细胞介素（IL）-6、IL-17A、肿瘤坏死因子（TNF）-α水平；Western blotting法检测各组中p-MST、p-YAP、p-Tafazzin蛋白（TAZ）、TEA域转录因子1（TEAD1）的蛋白表达量；流式细胞术检测外周血中Th17、Treg和Th17/Treg细胞比例。结果 与模型组比较，QSYQ组及XMU-MP-1组小鼠心肌梗死面积百分比均显著减小（P＜0.05、0.01）；心肌细胞结构损伤减轻，炎症细胞浸润减少，细胞凋亡数量减少；促炎因子IL-6、IL-17A、TNF-α水平显著降低（P＜0.05、0.01）；心脏组织p-MST、p-YAP、p-TAZ蛋白表达显著降低，TEAD1蛋白表达显著升高（P＜0.05、0.01）；外周血中Th17细胞比例降低，Th17/Treg动态平衡得到恢复（P＜0.05、0.01）。结论 QSYQ可能通过抑制MST/Hipp

Objective To explore the effects of Qishen Yiqi Dropping Pills on myocardial ischemia/reperfusion injury in mice through MST/Hippo signalling pathway.Methods Sixty C57BL/6J mice were randomly divided into six groups according to the random number table method: sham operation group, model group, XMU-MP-1 group (selectively inhibiting the MST target in the Hippo signaling pathway, 1 mg·kg^-1), and low-, medium-, and high-dose QSYQ groups (5.85, 11.70, and 23.40 g·kg^-1), with 15 mice in each group. Four weeks before modeling, mice in the QSYQ groups were intragastrically administered QSYQ (prepared as a suspension with distilled water) at 20 mL·kg^-1 once daily. Mice in the XMU-MP-1 group were intraperitoneally injected with XMU-MP-1 every other day for four weeks. Mice in the sham operation group and model group were ig administered the same volume of 0.9% sodium chloride solution. Except for the sham operation group, the mouse model of myocardial ischemia-reperfusion injury (MIRI) was established by ligating the left anterior descending coronary artery. After 30 min of ischemia and 2 h of reperfusion, the samples were collected. TTC staining was used to assess the myocardial infarction rate, HE staining to observe the pathological changes in cardiac tissue, TUNEL staining to evaluate myocardial cell apoptosis, and ELISA kits to detect the levels of serum inflammatory factors interleukin (IL)-6, IL-17A, and tumor necrosis factor (TNF)-α. Western blotting was used to detect the protein expression levels of pMST, p-YAP, p-Tafazzin (TAZ), and TEA domain transcription factor 1 (TEAD1) in each group. Flow cytometry was used to detect the proportions of Th17, Treg, and Th17/Treg cells in peripheral blood.Results Compared with the model group, the myocardial infarction rate in the QSYQ and XMU-MP-1 groups was significantly reduced (P<0.05, 0.01); Myocardial cell structural damage was alleviated, inflammatory cell infiltration was reduced, and the number of apoptotic cells decreased; the levels of pro-inflammatory factors IL-6, IL-17A, and TNF-α were significantly decreased (P<0.05, 0.01); The protein expression of p-MST, p-YAP, and p-TAZ in cardiac tissue was significantly decreased, and the protein expression of TEAD1 was significantly increased (P<0.05, 0.01); The proportion of Th17 cells in peripheral blood was decreased, and the dynamic balance of Th17/Treg was restored (P<0.05, 0.01).Conclusion QSYQ may exert a protective effect on MIRI by inhibiting the MST/Hippo signaling pathway.

R285.5

国家中医药传承创新中心项目（2023019-11）；广西自然科学基金会重点项目（2020GXNSFDA297020）；国家自然科学基金项目（81960861）；研究生教育创新计划项目（YCBXJ2023033）