目的 探索芪參益氣滴丸（QSYQ）通過MST/Hippo信號通路對小鼠心肌缺血再灌注損傷（MIRI）后炎癥反應的影響。方法 將60只C57BL/6J小鼠按隨機數(shù)字表法分為6組：假手術組、模型組、XMU-MP-1（選擇性抑制Hippo信號通路中的MST靶點，l mg·kg^-1）組和QSYQ低、中、高劑量（5.85、11.70、23.40 g·kg^-1）組，每組15只。造模前QSYQ組小鼠ig予以QSYQ（用蒸餾水配制成混懸液）4周，20 mL·kg^-1，每天給藥1次，XMU-MP-1組腹膜內(nèi)注射XMU-MP-1，每隔1 d給藥1次，連續(xù)給藥4周，假手術組和模型組ig給予等量0.9%氯化鈉溶液。除假手術組外，采用左冠狀動脈前降支結扎術制備小鼠MIRI模型，缺血30 min復灌2 h后取材。利用TTC染色評估心肌梗死面積百分比，HE染色觀察心臟組織病理改變，TUNEL染色評估心肌細胞凋亡情況，ELISA試劑盒檢測血清炎癥因子白細胞介素（IL）-6、IL-17A、腫瘤壞死因子（TNF）-α水平；Western blotting法檢測各組中p-MST、p-YAP、p-Tafazzin蛋白（TAZ）、TEA域轉錄因子1（TEAD1）的蛋白表達量；流式細胞術檢測外周血中Th17、Treg和Th17/Treg細胞比例。結果 與模型組比較，QSYQ組及XMU-MP-1組小鼠心肌梗死面積百分比均顯著減?。?i>P＜0.05、0.01）；心肌細胞結構損傷減輕，炎癥細胞浸潤減少，細胞凋亡數(shù)量減少；促炎因子IL-6、IL-17A、TNF-α水平顯著降低（P＜0.05、0.01）；心臟組織p-MST、p-YAP、p-TAZ蛋白表達顯著降低，TEAD1蛋白表達顯著升高（P＜0.05、0.01）；外周血中Th17細胞比例降低，Th17/Treg動態(tài)平衡得到恢復（P＜0.05、0.01）。結論 QSYQ可能通過抑制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

國家中醫(yī)藥傳承創(chuàng)新中心項目（2023019-11）；廣西自然科學基金會重點項目（2020GXNSFDA297020）；國家自然科學基金項目（81960861）；研究生教育創(chuàng)新計劃項目（YCBXJ2023033）