【目的】 探讨苓桂术甘汤对慢性心力衰竭（CHF）大鼠左心室心肌纤维化及磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT） 信号通路的影响。【方法】 采用冠状动脉结扎法建立CHF心肌纤维化大鼠模型。将大鼠按随机数字表法分为假手术组，模型 组，苓桂术甘汤低、中、高剂量组，卡托普利组，每组 10只。分组治疗结束后，对各组大鼠进行心脏超声评估心脏功能， 采用苏木精-伊红（HE）法观察心肌组织病理形态、计算心肌细胞横截面积，采用Masson染色法观察心肌组织胶原沉积情况， 并计算胶原沉积面积比例，采用酶联免疫吸附分析（ELISA）法检测心肌组织肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）水 平，Western Blot法检测心肌组织心肌纤维化标志物转化生长因子β1（TGF-β1）、α平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原蛋白 （collagen Ⅰ）、Ⅲ型胶原蛋白（collagen Ⅲ）蛋白和PI3K/AKT信号通路磷酸化的磷脂酰肌醇3-激酶（p-PI3K）、磷酸化的蛋白激 酶 B（p-AKT）和磷酸化的哺乳动物雷帕霉素靶蛋白（p-mTOR）表达水平。【结果】 与假手术组比较，模型组左心室射血分数 （LVEF）、左心室短轴缩短率（LVFS）水平显著降低，心肌细胞横截面积，胶原沉积面积比例，心肌组织TNF-α、IL-6水平及 TGF-β1、α-SMA、collagen Ⅰ、collagen Ⅲ、p-PI3K、p-AKT、p-mTOR水平显著升高，差异有统计学意义（P＜0.01）；与模 型组比较，卡托普利组，苓桂术甘汤中、高剂量组LVEF、LVFS显著升高，心肌细胞横截面积，胶原沉积面积比例，TNF-α、 IL-6水平及TGF-β1、α-SMA、collagen Ⅰ、collagen Ⅲ、p-PI3K、p-AKT、p-mTOR水平显著降低，差异有统计学意义（P＜ 0.01）；与卡托普利组比较，苓桂术甘汤高剂量组LVEF、LVFS显著升高，心肌细胞横截面积，胶原沉积面积比例，TNF-α、 IL-6 水平及 TGF-β1、α-SMA、collagen Ⅰ、collagen Ⅲ、p-PI3K、p-AKT、p-mTOR 水平显著降低，差异有统计学意义 （P＜0.01）。【结论】 苓桂术甘汤能够改善 CHF 大鼠左心室心肌纤维化和病理损伤，其机制可能与抑制 PI3K/AKT 信号通路 有关。

Objective To investigate the effects of Linggui Zhugan Decoction （LGZGD） on left ventricular myocardial fibrosis and the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway in rats with chronic heart failure （CHF）. Methods A rat model of CHF with myocardial fibrosis was established via coronary artery ligation. Rats were randomly divided into sham-operated，model，LGZGD low/medium/high-dose， and Captopril groups， with 10 rats in each group. After treatment， cardiac function was assessed by echocardiography. Myocardial histopathology was examined using hematoxylin-eosin （HE） staining （with cardiomyocyte cross-sectional area calculated），while collagen deposition was evaluated via Masson’s trichrome staining （collagen volume fraction quantified）. ELISA was used to measure myocardial TNF- α and IL-6 levels. Western Blot was used to analyze expression of fibrosis markers （TGF-β1，α-SMA，collagen I/III） and PI3K/AKT pathway components （p-PI3K，p-AKT，p-mTOR）. Results Compared with the sham-operated group，the model group showed significantly reduced LVEF and LVFS levels，as well as significantly increased myocardial cell cross-sectional area，collagen deposition area ratio，myocardial tissue TNF-α and IL-6 levels，and TGF-β1， α -SMA， collagen Ⅰ ， collagen Ⅲ ， p-PI3K， p-AKT， and p-mTOR levels， with statistically significant differences （P＜0.01）；compared with the model group，the Captopril group and the medium- and high-dose groups of LGZGD showed significantly increased LVEF and LVFS，as well as significantly increased myocardial cell cross-sectional area， collagen deposition area ratio， TNF- α and IL-6 levels， and TGF- β1， α -SMA， collagen Ⅰ，collagen Ⅲ，p-PI3K，p-AKT，and p-mTOR levels were significantly reduced，with statistically significant differences （P＜0.01）；compared with the Captopril group，the high-dose group of LGZGD showed a significant increase in LVEF and LVFS，as well as a significant decrease in myocardial cell cross-sectional area， collagen deposition area ratio，TNF-α，IL-6 levels，and TGF-β1，α-SMA，collagen Ⅰ，collagen Ⅲ，p-PI3K， p-AKT， and p-mTOR levels were significantly reduced， with statistically significant differences （P＜0.01）. Conclusion LGZGD ameliorates left ventricular myocardial fibrosis and pathological damage in CHF rats， potentially through inhibition of the PI3K/AKT signaling pathway.

R285.5

江苏省优势学科建设工程项目（编号：YSHL2202-181）