目的 基于cGAS/STING 信号通路探讨心康冲剂对慢性心力衰竭大鼠炎症因子的干预作用及分子机制。 方法 将SD 大鼠随机分为正常组、造模组，通过腹腔注射盐酸阿霉素建立慢性心力衰竭模型，待模型成功后 再分为模型组、缬沙坦组、心康冲剂组。模型组每日灌胃蒸馏水，缬沙坦组每日以缬沙坦溶液灌胃，心康冲剂 组每日灌胃心康冲剂溶液治疗，连续4 周。采用超声心动图检测各组大鼠心功能；苏木素-伊红染色（HE）检测 各组大鼠心肌病理学改变；透射电镜观察各组大鼠心肌超微结构改变；采用酶联免疫吸附测定法（ELISA）检测 各组大鼠血清中白细胞介素1β（IL-1β）、白细胞介素6（IL-6）含量；实时荧光定量法（qPCR）检测各组大鼠心肌 组织中线粒体转录因子A（TFAM）、环化鸟苷酸-腺苷酸合成酶（cGAS）、干扰素刺激基因（STING）、IL-6 mRNA 的表达水平。免疫组化法检测大鼠心肌组织cGAS、STING 蛋白表达。结果 与空白组比较，模型组大鼠心肌 炎性细胞浸润明显，可见炎性水肿；心功能明显降低（P＜0.05，P＜0.01），血清炎症因子明显升高（P＜0.01）， 心肌组织中TFAM mRNA 表达明显降低（P＜0.01），IL-6、cGAS、STING mRNA 表达明显上调（P＜0.01），心 肌组织中cGAS、STING 蛋白明显增加（P＜0.01）。与模型组比较，心康冲剂组大鼠心功能明显改善（P＜0.05， P＜0.01）；心肌细胞炎性浸润减轻；血清炎性因子表达明显降低（P＜0.01），心肌组织中TFAM mRNA 表达明 显增加（P＜0.05），IL-6、cGAS、STING mRNA 表达明显下调（P＜0.01）；心肌组织中cGAS、STING 蛋白表达 明显下调（P＜0.01）。结论 心康冲剂可降低慢性心力衰竭大鼠炎性因子表达，改善心功能，其机制可能与抑 制cGAS/STING 信号通路有关。

Abstract： Objective To explore the intervention effect and molecular mechanism of Xinkang Granules on inflammatory factors in rats with chronic heart failure based on cGAS/STING signaling pathway. Methods SD rats were randomly divided into normal group and modeling group. The chronic heart failure model was established by intraperitoneal injection of Doxorubicin Hydrochloride. After successfully modeling，the rats were further divided into model group，Valsartan group and Xinkang Granules group. The model group was treated with distilled water every day，the Valsartan group was treated with Valsartan solution every day，and the Xinkang Granules group was treated with Xinkang Granules every day， all given for 4 consecutive weeks. Echocardiography was used to detect cardiac function， the pathological changes of myocardium were detected by hematoxylin-eosin staining （HE）， the ultrastructural changes of myocardium in each group were observed by transmission electron microscope， and the contents of interleukin-1β （IL-1β） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of mitochondrial transcription factor A （TFAM）， cyclic guanosine monophosphate-adenylate synthase （cGAS）， interferon-stimulated gene （STING） and IL-6 in myocardial tissue of rats in each group were detected by real-time fluorescence quantitative method （qPCR） . The protein expressions of cGAS and STING in rat myocardial tissue were detected by immunohistochemical method. Results Compared with the blank group， the rats in the model group had significant inflammatory cell infiltration and inflammatory edema in myocardial tissue，their cardiac function was significantly reduced （P＜0.05，P＜0.01）， and serum inflammatory factors were significantly increased （P＜0.01）. The mRNA expression of TFAM in myocardial tissue was significantly reduced （P＜0.01），the mRNA expressions of IL-6，cGAS，and STING were significantly increased （P＜0.01）， and the protein expressions of cGAS and STING in the myocardial tissue were significantly increased （P＜0.01）. Compared with the model group，the cardiac function of the rats in the Xinkang Granules group was significantly improved （P＜0.05， P＜0.01）， the inflammatory infiltration of myocardial cells was reduced， the expression of serum inflammatory factors was significantly reduced （P＜0.01）， the mRNA expression of TFAM in myocardial tissue was significantly increased （P＜0.05），and the mRNA expressions of IL- 6， cGAS， and STING were significantly decreased （P＜0.01）， the protein expressions of cGAS and STING in myocardial tissue were significantly decreased （P＜0.01）. Conclusion Xinkang Granules can reduce the expression of inflammatory factors and improve cardiac function in rats with chronic heart failure. Its mechanism may be related to inhibiting the cGAS/STING signaling pathway.

R285.5

湖南省中医药科研计划项目（CX2022004）；湖南省卫健委科研计划项目（D202303017511）；湖南中医药大学“一方”研究生创新项目 （2023YF08）；湖南中医药大学研究生创新项目（2023CX20）