目的 基于 JAK2/STAT3 通路，探讨中药复方金欣康对心力衰竭（简称心衰）小鼠心肌纤维化的作用和机 制。方法 90 只 SPF 级雄性 C57BL/6J 小鼠随机分为假手术组、模型组、金欣康低剂量组、金欣康中剂量组、 金欣康高剂量组和卡托普利组，每组 15 只，采用结扎小鼠冠状动脉前降支（LAD）复制心衰模型。给药 4 周后， 采用心脏彩超评估心脏结构功能改变，以 HE 染色、MASSON 染色和天狼星红染色观察心肌病理变化与纤维化 程度，qPCR 法检测心肌纤维化标记物与心衰标记物的 mRNA 表达，Elisa 法测定血清中氨基末端 B 型利钠肽 前体（NT-proBNP）及炎症因子水平，Western Blot 法检测心肌组织 JAK2/STAT3 通路相关蛋白的表达，免疫荧 光染色心肌组织检测通路关键蛋白 pSTAT3 的表达与细胞定位。结果 与假手术组比较，模型组左室射血分数 （LVEF）、缩短分数（LVFS）显著降低，舒张期左心室内径（LVIDd）、收缩期左心室内径（LVIDs）显著升高（P＜ 0.01）；心肌组织切片可观察到心肌组织水肿，细胞核缺失，心肌纤维断裂和紊乱，梗死区周围炎症细胞浸润 与纤维组织沉积，染色胶原容积分数与 I 型胶原纤维占比明显增加（P＜0.01）。与模型组比较，金欣康给药组 与卡托普利组 LVEF、LVFS 提高（P＜0.01，P＜0.05），LVIDs、LVIDd 显著降低（P＜0.01）；心肌组织切片可观 察到心肌组织损伤有所改善，胶原纤维沉积减少，心肌纤维化减轻；染色胶原容积分数与 I 型胶原纤维占比明 显减少（P＜0.01）；小鼠血清中 NT-proBNP、TNF-α、IL-6、IL-1β 水平明显下降（P＜0.01），IL-10 明显升高 （P＜0.01）；小鼠心肌 Nppa、Nppb、Col1a1、Col1a2、Col3a1、Acta2、Tgfb1 的 mRNA 表达量减少（P＜0.01， P＜0.05），α-SMA、MMP-2、MMP-9 的蛋白表达下降（P＜0.01，P＜0.05），通路蛋白 p-STAT3/STAT3、 p-JAK2/JAK2 的比值下降（P＜0.01，P＜0.05）；p-STAT3 蛋白相对荧光强度与 p-STAT3 在细胞核/细胞质内的 荧光强度比值降低（P＜0.01，P＜0.05）。结论 金欣康可有效减轻 LAD 结扎心衰小鼠心肌纤维化与炎症反应， 改善心功能，抑制心室重构；其作用机制可能与抑制 JAK2/STAT3 通路相关。

Objective To investigate the effects and mechanisms of the traditional Chinese medicine compound Jinxinkang on myocardial fibrosis in heart failure （HF） mice based on the JAK2/STAT3 signaling pathway. Methods Ninety SPF-grade male C57BL/6J mice were randomly divided into sham-operated， model， Jinxinkang low-dose，Jinxinkang medium-dose，Jinxinkang high-dose，and Captopril groups （n=15 per group）. HF was induced by ligating the left anterior descending coronary artery （LAD）. After 4 weeks of treatment， cardiac structure and function were assessed via echocardiography. Myocardial pathology and fibrosis were evaluated using HE staining，MASSON staining， and Sirius red staining. mRNA expression of fibrosis and HF markers was quantified by qPCR. Serum levels of NTproBNP and inflammatory cytokines were measured by ELISA. Protein expression of JAK2/STAT3 pathway components was detected by Western Blot，fibrosis-related proteins p-STAT3 localization were analyzed by immunofluorescence. Results Compared with the sham-operated group， the model group showed significantly decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS），while exhibiting significantly increased left ventricular internal diameter at end-diastole （LVIDd） and left ventricular internal diameter at end-systole （LVIDs） （P＜0.01）； myocardial tissue sections revealed myocardial edema， nuclear loss， myocardial fiber rupture and disarray， inflammatory cell infiltration around the infarct zone with fibrous tissue deposition， and significantly increased collagen volume fraction and type I collagen fiber proportion （P＜0.01）. Compared with the model group， both the Jinxinkang treatment group and Captopril group demonstrated improved LVEF and LVFS （P＜0.01， P＜ 0.05）， with significantly reduced LVIDs and LVIDd （P＜0.01）； myocardial tissue sections showed alleviated myocardial injury，decreased collagen fiber deposition，and reduced myocardial fibrosis；collagen volume fraction and type I collagen fiber proportion were significantly decreased （P＜0.01）；serum levels of NT-proBNP，TNF-α，IL-6， and IL-1β were markedly reduced （P＜0.01），while IL-10 was significantly increased （P＜0.01）；myocardial mRNA expression of Nppa， Nppb， Col1a1， Col1a2， Col3a1， Acta2， and Tgfb1 was decreased （P＜0.01， P＜0.05）， protein expression of α-SMA，MMP-2，and MMP-9 was reduced （P＜0.01，P＜0.05），and the ratios of pathway proteins p-STAT3/STAT3 and p-JAK2/JAK2 were decreased （P＜0.01，P＜0.05）；the relative fluorescence intensity of p-STAT3 protein and the nuclear/cytoplasmic fluorescence intensity ratio of p-STAT3 were decreased （P＜0.01，P＜ 0.05）. Conclusion Jinxinkang ameliorates myocardial fibrosis， inflammatory response， cardiac function and ventricular remodeling in LAD-induced HF mice，potentially via JAK2/STAT3 pathway inhibition.

R285.5

国家中医药传承创新中心科研专项重点项目（2023ZD08）；广州中医药大学中医基础理论研究“揭榜挂帅”项目（A1-2606-23-415-110Z15）； 国家重点研发计划项目（2022YFC3500101，2022YFC3500103）；广东省基础与应用基础研究基金项目（2021A1515220046，2023A1515220070）。