目的 研究隱丹參酮對急性心肌梗死后心室重構(gòu)的保護(hù)作用，并研究其可能的機(jī)制。方法 采用左前降支冠狀動脈結(jié)扎術(shù)構(gòu)建急性心肌梗死模型，將60只雄性C57BL/6小鼠隨機(jī)分為假手術(shù)組、模型組、氯沙坦鉀（陽性藥，15 mg∙kg^-1）和隱丹參酮低、高劑量（21、63 mg∙kg^-1）組，每組12只，術(shù)后1 h給藥，連續(xù)給藥7 d；小動物超聲檢測心臟功能，TTC染色檢測心肌梗死面積，蘇木素-伊紅（HE）染色檢測心臟形態(tài)學(xué)變化，免疫組化檢測纖維化相關(guān)蛋白肌動蛋白α（α-SMA）、I型膠原蛋白（Col I）的表達(dá)，生化儀檢測血清中乳酸脫氫酶（LDH）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）和心肌肌鈣蛋白T（cTnT）的水平，Western blotting檢測轉(zhuǎn)化生長因子β1（TGF-β1）/Smad3信號通路相關(guān)蛋白的表達(dá)。結(jié)果 與假手術(shù)組相比，模型組小鼠心臟功能顯著降低（P＜0.01），心肌梗死面積顯著增加（P＜0.01），心肌細(xì)胞排列混亂，大量炎癥細(xì)胞浸潤，血清中LDH、CK、CK-MB、ALT、AST和cTnT的水平均顯著增加（P＜0.01）；纖維化標(biāo)志蛋白α-SMA、Col Ⅰ的表達(dá)增加（P＜0.01），TGF-β1、p-Smad3的表達(dá)增加（P＜0.01）；與模型組比較，高劑量隱丹參酮和氯沙坦鉀均可顯著改善急性心肌梗死小鼠的心臟功能（P＜0.05），降低心肌梗死面積（P＜0.01），減少心肌細(xì)胞中炎癥細(xì)胞浸潤，降低血清LDH、CK、CK-MB、ALT、AST和cTnT水平（P＜0.01），降低α-SMA、Col Ⅰ、TGF-β1、p-Smad3蛋白表達(dá)（P＜0.01）。結(jié)論 隱丹參酮可能通過抑制急性心肌梗死小鼠心肌細(xì)胞中TGF-β/Smad3信號通路，減少心肌纖維化和心肌梗死面積，改善心臟功能，減少心室重構(gòu)。

Objective To explore the preventive effect and mechanism of cryptotanshinone on ventricular remodeling after acute myocardial infarction in mice. Methods Acute myocardial infarction model was established by ligation of left anterior descending coronary artery. Sixty male C57BL/6 mice were randomly divided into a sham operation group, a model group, losartan potassium (positive drug, 15 mg∙kg^-1), and low and high doses of cryptotanshinone (21, 63 mg∙kg^-1) groups, with 12 mice in each group. The drug was administered 1 h after surgery, and continuously for 7 d. Cardiac ultrasound was used to detect cardiac function, TTC staining was used to detect myocardial infarction size, HE staining was used to detect cardiac morphological changes, immunohistochemistry was used to detect the expression of α-SMA and Col Ⅰ proteins associated with myocardial fibrosis, the contents of biochemical indicators in serum were detected, and Western blotting was used to detect the expression of TGF-β/Smad3 signaling pathway related proteins. Results Compared with the sham operation group, the cardiac function was significantly decreased in model group (P < 0.01), myocardial infarction area was significantly increased (P < 0.01), myocardial cells were disordered, a large number of inflammatory cells infiltrated, the serum of LDH, CK, CK-MB, ALT, AST and cTnT were significantly increased (P < 0.01), the expressions of α-SMA and Col Ⅰ were significantly increased (P < 0.01), and the expressions of TGF-β1 and p-Smad3 were significantly increased (P < 0.01). Compared with the model group, both the high-dose cryptotanshinone and the losartan could significantly improve the cardiac function of mice with acute myocardial infarction (P < 0.05), reduced the myocardial infarction size (P < 0.01), reduced the inflammatory cell infiltration in myocardial cells, reduced the contents of LDH, CK, CK-MB, ALT, AST and cTnT (P < 0.01), and reduced the expression of α-SMA, Col Ⅰ, TGF-β1 and p-Smad3 (P < 0.01). Conclusion Cryptotanshinone could reduce myocardial fibrosis and myocardial infarction size, improve ventricular remodeling and cardiac function by inhibiting TGF-β/Smad3 signaling pathway in myocardial cells of mice with acute myocardial infarction.

R285.5

中國博士后科學(xué)基金（2023M740790）；廣東省重點(diǎn)領(lǐng)域研發(fā)計(jì)劃項(xiàng)目（No.2020B1111110002）；廣州市青年人才托舉工程項(xiàng)目（QT20220101283）