目的 基于NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）炎症小体探讨三七龙血竭胶囊干预心梗后心室重构大鼠的作用及机制。方法 雄性SD大鼠通过冠状动脉左前降支结扎法构建心梗模型，随机分为模型组及三七龙血竭低、高剂量（0.17、0.34 g/kg）组和厄贝沙坦（6.6 mg/kg）组，每组12只，另取12只正常大鼠作为假手术组。术后第3天开始连续给药2周，心脏超声检测大鼠左室舒张末期内径（left ventricular end-diastolic dimension，LVEDD）、左室收缩末期内径（left ventricular end-systolic dimension，LVESD）、左室舒张末期容积（left ventricular end-diastolic volume，LVEDV）、左室收缩末期容积（left ventricular end-systolic volume，LVESV）、射血分数（ejection fraction，EF）和收缩分数（fractional shortening，FS）；心脏称定质量计算心脏指数；ELISA法检测血清中脑钠肽（brain natriuretic peptide，BNP）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）水平；TTC染色观察心梗面积；采用苏木素-伊红（HE）和Masson染色观察大鼠心肌组织病理改变及纤维化程度；Western blotting和qRT-PCR测定心肌组织钙敏感受体（calcium sensing receptor，CaSR）、NLRP3、半胱氨酸天冬氨酸蛋白酶-1（cystein-asparate protease-1，Caspase-1）、Gasdermin D（GSDMD）、IL-1β、IL-18 mRNA及蛋白的表达。结果 与模型组比较，三七龙血竭胶囊可显著抑制大鼠心肌梗死面积（P＜0.05、0.01），降低心脏指数（P＜0.05），减轻心肌组织心肌细胞排列紊乱、炎症细胞浸润等病理改变，降低心肌纤维化程度（P＜0.01）；显著提高心梗大鼠EF和FS（P＜0.05、0.01），降低LVEDD、LVESD、LVESV、LVEDV及血清中BNP、TNF-α、IL-1β水平（P＜0.05、0.01），改善心功能及心室重构；显著降低心梗大鼠心肌组织CaSR、NLRP3、Caspase-1、GSDMD、IL-1β、IL-18 mRNA及蛋白的表达（P＜0.05、0.01）。结论 三七龙血竭胶囊能够显著抑制心梗大鼠心肌组织炎症及纤维化程度，延缓心肌损伤及心室重构，改善心脏功能，其作用机制可能与抑制CaSR介导的NLRP3炎症小体引发的炎症反应有关。

Objective To investigate the effect and mechanism of Sanqi Longxuejie Capsules (三七龙血竭胶囊) on post-myocardial infarction ventricular remodeling in rats based on NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory pathway. Methods Male SD rats were used to construct a myocardial infarction model by ligating the left anterior descending branch of the coronary artery, and randomly divided into model group, Sanqi Longxuejie Capsules low-, high-dose (0.17, 0.34 g/kg) groups and irbesartan (6.6 mg/kg) group, with 12 rats in each group. Additionally, 12 normal rats were selected as sham group. Starting from the third day after surgery, continuous medication was administered for two weeks. Echocardiography was performed to evaluate left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), ejection fraction (EF) and fractional shortening (FS). The heart index was calculated using heart weight normalized by the body weight. Levels of brain natriuretic peptide (BNP), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum were detected by ELISA. TTC staining was used to observe the area of myocardial infarction; Hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes and fibrosis degree of myocardial tissue; Western blotting and qRT-PCR were used to measure the expressions of calcium sensing receptor (CaSR), NLRP3, cysteine aspartate protease-1 (Caspase-1), Gasdermin D (GSDMD), IL-1β, IL-18 mRNA and protein in myocardial tissue. Results Compared with model group, Sanqi Longxuejie Capsules significantly inhibited myocardial infarction area in rats (P < 0.05, 0.01), reduced cardiac index (P < 0.05), alleviated pathological changes such as disordered arrangement of myocardial cells and infiltration of inflammatory cells in myocardial tissue, and reduced the degree of myocardial fibrosis (P < 0.01), significantly increased EF and FS in myocardial infarction rats (P < 0.05, 0.01), decreased LVEDD, LVESD, LVESV, LVEDV, and levels of BNP, TNF-α, IL-1β in serum (P < 0.05, 0.01), improved cardiac function and ventricular remodeling, significantly reduced the expressions of CaSR, NLRP3, Caspase-1, GSDMD, IL-1β, IL-18 mRNA and protein in myocardial tissue of myocardial infarction rats (P < 0.05, 0.01). Conclusion Sanqi Longxuejie Capsules could significantly inhibit the inflammation and fibrosis of myocardial tissue in myocardial infarction rats, delay myocardial injury and ventricular remodeling, and improve cardiac function. Its mechanism may be related to the inhibition of inflammation caused by CaSR mediated NLRP3 inflammasome.

R285.5

国家自然科学基金面上项目（82374413）