目的 基于NOD樣受體熱蛋白結構域相關蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）炎癥小體探討三七龍血竭膠囊干預心梗后心室重構大鼠的作用及機制。方法 雄性SD大鼠通過冠狀動脈左前降支結扎法構建心梗模型，隨機分為模型組及三七龍血竭低、高劑量（0.17、0.34 g/kg）組和厄貝沙坦（6.6 mg/kg）組，每組12只，另取12只正常大鼠作為假手術組。術后第3天開始連續(xù)給藥2周，心臟超聲檢測大鼠左室舒張末期內徑（left ventricular end-diastolic dimension，LVEDD）、左室收縮末期內徑（left ventricular end-systolic dimension，LVESD）、左室舒張末期容積（left ventricular end-diastolic volume，LVEDV）、左室收縮末期容積（left ventricular end-systolic volume，LVESV）、射血分數(shù)（ejection fraction，EF）和收縮分數(shù)（fractional shortening，F(xiàn)S）；心臟稱定質量計算心臟指數(shù)；ELISA法檢測血清中腦鈉肽（brain natriuretic peptide，BNP）、腫瘤壞死因子-α（tumor necrosis factor-α，TNF-α）、白細胞介素-1β（interleukin-1β，IL-1β）水平；TTC染色觀察心梗面積；采用蘇木素-伊紅（HE）和Masson染色觀察大鼠心肌組織病理改變及纖維化程度；Western blotting和qRT-PCR測定心肌組織鈣敏感受體（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及蛋白的表達。結果 與模型組比較，三七龍血竭膠囊可顯著抑制大鼠心肌梗死面積（P＜0.05、0.01），降低心臟指數(shù)（P＜0.05），減輕心肌組織心肌細胞排列紊亂、炎癥細胞浸潤等病理改變，降低心肌纖維化程度（P＜0.01）；顯著提高心梗大鼠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構；顯著降低心梗大鼠心肌組織CaSR、NLRP3、Caspase-1、GSDMD、IL-1β、IL-18 mRNA及蛋白的表達（P＜0.05、0.01）。結論 三七龍血竭膠囊能夠顯著抑制心梗大鼠心肌組織炎癥及纖維化程度，延緩心肌損傷及心室重構，改善心臟功能，其作用機制可能與抑制CaSR介導的NLRP3炎癥小體引發(fā)的炎癥反應有關。

Objective To investigate the effect and mechanism of Sanqi Longxuejie Capsules (三七龍血竭膠囊) 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

國家自然科學基金面上項目（82374413）