目的 基于巨噬细胞极化调控心肌细胞代谢重塑探讨暖心康 （红参、毛冬青） 改善心肌梗死小鼠心肌纤维化的机制。方法 （1） 将 C57BL/6J 雄性小鼠随机分为 3 组：假手术组、模型组、暖心康组 （1.65 g•kg-1） ，每组10 只。采用结扎冠状动脉术复制心肌梗死小鼠模型。灌胃给药，每日 1 次，连续 4 周。采用 Masson 染色法检测心肌组织纤维化；qPCR 法检测心脏组织中 LDHA、HK2、CD36、CPT-1A、PPAR-γ、PGC-1α、Ndufa8、SDHd、Cyc1、Cox4i2、CD86、iNOS、TNF-α mRNA 表达水平；ELISA 法检测血清炎症因子 IL-1β 的水平。（2） 采用脂多糖诱导 RAW264.7 巨噬细胞向促炎型巨噬细胞极化，制备促炎型巨噬细胞上清液，将其作用于HL-1 心肌细胞模型。HL-1 心肌细胞分组与 RAW264.7 巨噬细胞分组相同：空白血清对照组 （含 5% 空白血清+5% 胎牛血清的培养基） 、暖心康含药血清组 （含 5% 暖心康含药血清+5% 胎牛血清的培养基） 、脂多糖组 （含5% 空白血清+5% 胎牛血清的培养基+200 μg•mL-1脂多糖） 和暖心康含药血清+脂多糖组 （含 5% 暖心康含药血清+5% 胎牛血清的培养基+200 μg•mL-1脂多糖） ，均干预 24 h。采用油红 O 染色检测心肌细胞中脂质分布情况；DCFH-DA 荧光探针检测细胞 ROS 水平。结果 （1） 与模型组比较，暖心康组小鼠心脏组织胶原沉积面积显著减少 （P＜0.01） ，且梗死区域局部室壁损伤程度减轻；心脏组织中 LDHA、HK2、CD36、CPT-1A、PPAR-γ、Ndufa8、SDHd、Cyc1、Cox4i2、CD86、iNOS、TNF- α mRNA 表达水平显著降低（P＜0.05，P＜0.01，P＜0.001） ，PGC-1α mRNA 表达水平明显升高 （P＜0.05） ；血清 IL-1β 水平显著降低 （P＜0.001） 。 （2） 与脂多糖组比较，暖心康含药血清+脂多糖组 HL-1 心肌细胞胞浆内的脂滴沉积明显减少 （P＜0.05） ，ROS 水平显著降低 （P＜0.001） 。结论 暖心康能够减轻心肌梗死小鼠的心肌纤维化及心室重构，其作用机制可能与抑制促炎型巨噬细胞极化，降低炎症水平，减少 ROS 生成，降低心脏组织糖酵解水平，改善氧化磷酸化和脂肪酸代谢有关。

Objective To explore the mechanism of Nuanxinkang （NXK，composed of Ginseng Radix et Rhizoma Rubra and Ilex Pubescen） on alleviating myocardial fibrosis in mice with myocardial infarction by orchestrating myocardial cell metabolic remodeling based on macrophage polarization. Methods （1） C57BL/6J male mice were randomly divided into three groups：sham operation group，model group and NXK administration group（1.65 g•kg-1），with 10 rats in each group. The myocardial infarction model of mice was induced by ligating coronary artery. The drug administration group was given NXK once a day for four weeks. Masson staining was used to detect myocardial fibrosis，and quantitative PCR was used to detect the mRNA expression levels of LDHA，HK2，CD36，CPT-1A，PPAR-γ，PGC-1α，Ndufa8，SDHd，Cyc1，Cox4i2，CD86，iNOS and TNF-α in cardiac tissues. The content of inflammatory factor IL-1β in serum was detected by ELISA.（2） Lipopolysaccharide （LPS） was used to induce the polarization of RAW264.7 macrophages into pro-inflammatory subtype. The supernatant fluid of pro-inflammatory macrophages was prepared and subsequently acted on HL-1 cardiomyocytes. RAW264.7 macrophages and HL-1 cardiomyocytes were divided into control serum group（culture medium with 5% blank serum and 5% fetal bovine serum），NXK-contained serum group （culture medium with 5% NXK-contained serum and 5% fetal bovine serum），LPS treatment group（culture medium with 5% blank serum，5% fetal bovine serum and 200 μg•mL-1 LPS） and NXK-contained serum+LPS treatment group （culture medium with 5% NXK-contained serum，5% fetal bovine serum and 200 μg•mL-1 LPS）. After 24-h intervention in each group，the lipid in the cells was labeled by Oil Red O staining，and the reactive oxygen species （ROS） level of the cells was detected by DCFH-DA fluorescent probe. Results （1） Compared with the model group，collagen deposition area in cardiac tissue of mice was remarkably reduced （P＜0.01） and local ventricular wall damage in the infarcted area was alleviated in NXK group. Also，the mRNA expressions of LDHA，HK2，CD36，CPT-1A，PPAR-γ，Ndufa8，SDHd，Cyc1，Cox4i2，CD86，iNOS and TNF-α were significantly decreased （P＜0.05，P＜0.01，P＜0.001）. The mRNA expression of PGC-1α was significantly increased （P＜0.05）. Serum IL-1β level was obviously decreased（P＜0.001）.（2）Compared with the LPS group，the deposition of lipid droplets in cytoplasm of HL-1 cardiomyocytes in NXK-contained serum + LPS treatment group was remarkably reduced （P＜0.05） and ROS level decreased significantly （P＜0.001）. Conclusion NXK can alleviate myocardial fibrosis and ventricular remodeling after myocardial infarction in mice，and its mechanism may be related to inhibiting the polarization of pro-inflammatory macrophages，alleviating inflammation level，reducing the production of ROS，reducing the level of glycolysis in cardiac tissue，and improving oxidative phosphorylation and fatty acid metabolism.

R285.5

国家自然科学基金青年项目 （82004293）