目的 基于 PTEN/AKT/mTOR 通路探讨补心泻肺方改善慢性心力衰竭（CHF）小鼠心肌纤维化的作用及分 子机制。方法 采用腹腔注射盐酸异丙肾上腺素（5 mg·kg-1 ，每日 2 次，共 14 d）建立 C57/BL6J 小鼠慢性心力 衰竭模型，将小鼠随机分为对照组、模型组及补心泻肺方低（2.9 g·kg-1 ）、中（5.8 g·kg-1 ）、高（11.6 g·kg-1 ）剂量 组和培哚普利组（0.41 mg·kg-1 ）。补心泻肺方各剂量组和培哚普利组灌胃相应药物，对照组和模型组灌胃等体 积生理盐水，共 4 周。采用小动物心脏彩超检测左心室射血分数（LVEF）、左室短轴缩短率（LVFS）、左心室舒 张末期容积（LVEDV）、左心室收缩末期容积（LVESV）、左心室舒张末期内径（LVEDD）和左心室收缩末期内径 （LVESD）水平；HE 染色法观察小鼠心脏组织病理变化；Masson 染色观察心肌纤维化变化；qRT-PCR 法检测 心脏组织中 α-SMA、Collagen Ⅰ和 Collagen Ⅲ mRNA 表达水平；Western Blot 法检测心脏组织 α-SMA、 Collagen Ⅰ、Collagen III、PTEN、p-AKT、p-mTOR、AKT、mTOR 蛋白表达水平。结果 （1）与对照组比较， 模型组小鼠的 LVEF 和 LVFS 值明显降低（P＜0.01），LVEDD、LVESD、LVEDV 和 LVESV 值明显升高（P＜ 0.01）；HE 染色显示模型组小鼠的心肌细胞边缘界限不清晰，细胞肿胀，局部炎症细胞浸润；Masson 染色显示 心肌纤维沉积；心脏组织 α-SMA，Collagen Ⅰ和 Collagen Ⅲ的 mRNA 和蛋白表达水平均明显升高（P＜0.01）； PTEN 蛋白表达水平明显升高（P＜0.01），p-AKT/AKT、p-mTOR/mTOR 比值明显降低（P＜0.01）。（2）与模型组 比较，补心泻肺方低、中、高剂量组小鼠的 LVEF、LVFS 值明显升高（P＜0.01），LVEDD、LVESD、LVEDV 和 LVESV 值明显降低（P＜0.01）；心脏组织病理损伤和纤维化明显改善；心脏组织 α-SMA、Collagen Ⅰ和 Collagen Ⅲ的 mRNA 和蛋白表达水平均明显降低（P＜0.01）；PTEN 蛋白表达水平明显降低（P＜0.01），p-AKT/ AKT 和 p-mTOR/mTOR 比值明显升高（P＜0.01）。结论 补心泻肺方能够有效改善慢性心力衰竭小鼠心功能， 抑制心室重构，其作用机制可能与调节 PTEN/AKT/mTOR 信号通路介导的心肌纤维化有关。

Objective To investigate the effect and molecular mechanism of Buxin Xiefei Formula （BXXF） in improving myocardial fibrosis in mice with chronic heart failure （CHF） based on the PTEN/AKT/mTOR pathway. Methods A CHF model was established in C57/BL6J mice by intraperitoneal injection of isoproterenol hydrochloride （5 mg·kg-1 ，twice daily for 14 days）. The mice were randomly divided into a control group，model group，low-dose BXXF （2.9 g·kg-1 ）， medium-dose BXXF （5.8 g·kg-1 ），and high-dose BXXF group （11.6 g·kg-1 ），and a perindopril group （0.41 mg·kg-1 ）. The BXXF groups and perindopril group were administered the corresponding drugs by gavage，while the control and model groups received an equal volume of saline for 4 weeks. Cardiac function was assessed using small-animal echocardiography to measure left ventricular ejection fraction （LVEF），left ventricular fractional shortening （LVFS）， left ventricular end-diastolic volume （LVEDV），left ventricular end-systolic volume （LVESV），left ventricular enddiastolic diameter （LVEDD）， and left ventricular end-systolic diameter （LVESD）. Pathological changes in cardiac tissue were observed by HE staining， while myocardial fibrosis was evaluated by Masson staining. The mRNA expression levels of α-SMA，Collagen Ⅰ，and Collagen Ⅲ in cardiac tissue were detected by qRT-PCR，and the protein expression levels of α -SMA，Collagen Ⅰ，Collagen Ⅲ，PTEN，p-AKT，p-mTOR，AKT，and mTOR were measured by Western Blot. Results （1） Compared with the control group，the model group showed significantly decreased LVEF and LVFS values （P＜0.01） and significantly increased LVEDD，LVESD，LVEDV，and LVESV values （P＜0.01）. HE staining revealed unclear myocardial cell boundaries，cell swelling，and local inflammatory cell infiltration in the model group. Masson staining indicated myocardial collagen deposition. The mRNA and protein expression levels of α-SMA，Collagen Ⅰ，and Collagen Ⅲ in cardiac tissue were significantly increased （P＜0.01）. PTEN protein expression was significantly elevated （P＜0.01），while the p-AKT/AKT and p-mTOR/mTOR ratios were significantly decreased （P＜0.01）.（2） Compared with the model group，the low-，medium-，and high-dose BXXF groups exhibited significantly increased LVEF and LVFS （P＜0.01） and significantly decreased LVEDD， LVESD， LVEDV， and LVESV （P＜0.01）. Pathological damage and fibrosis in cardiac tissue were markedly improved. The mRNA and protein expression levels of α -SMA， Collagen Ⅰ ， and Collagen Ⅲ were significantly decreased （P＜ 0.01）. PTEN protein expression was significantly reduced （P＜0.01）， while the p-AKT/AKT and p-mTOR/mTOR ratios were significantly increased （P＜0.01）. Conclusion BXXF effectively improves cardiac function and inhibits ventricular remodeling in mice with CHF， and its mechanism may be associated with the regulation of PTEN/AKT/ mTOR signaling pathway-mediated myocardial fibrosis.

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国家自然科学基金-青年科学基金项目（82405259）；广东省医学科学技术研究基金项目（A2024041）；广东省第二中医院科研创新基金 项目-基础与应用基础研究青年启航项目（SEZYY2023A10）；广东省第二中医院科研创新基金项目（SEZYY2023B18）。