[关键词]
[摘要]
目的 研究隐丹参酮对急性心肌梗死后心室重构的保护作用,并研究其可能的机制。方法 采用左前降支冠状动脉结扎术构建急性心肌梗死模型,将60只雄性C57BL/6小鼠随机分为假手术组、模型组、氯沙坦钾(阳性药,15 mg∙kg-1)和隐丹参酮低、高剂量(21、63 mg∙kg-1)组,每组12只,术后1 h给药,连续给药7 d;小动物超声检测心脏功能,TTC染色检测心肌梗死面积,苏木素-伊红(HE)染色检测心脏形态学变化,免疫组化检测纤维化相关蛋白肌动蛋白α(α-SMA)、I型胶原蛋白(Col I)的表达,生化仪检测血清中乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和心肌肌钙蛋白T(cTnT)的水平,Western blotting检测转化生长因子β1(TGF-β1)/Smad3信号通路相关蛋白的表达。结果 与假手术组相比,模型组小鼠心脏功能显著降低(P<0.01),心肌梗死面积显著增加(P<0.01),心肌细胞排列混乱,大量炎症细胞浸润,血清中LDH、CK、CK-MB、ALT、AST和cTnT的水平均显著增加(P<0.01);纤维化标志蛋白α-SMA、Col Ⅰ的表达增加(P<0.01),TGF-β1、p-Smad3的表达增加(P<0.01);与模型组比较,高剂量隐丹参酮和氯沙坦钾均可显著改善急性心肌梗死小鼠的心脏功能(P<0.05),降低心肌梗死面积(P<0.01),减少心肌细胞中炎症细胞浸润,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蛋白表达(P<0.01)。结论 隐丹参酮可能通过抑制急性心肌梗死小鼠心肌细胞中TGF-β/Smad3信号通路,减少心肌纤维化和心肌梗死面积,改善心脏功能,减少心室重构。
[Key word]
[Abstract]
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.
[中图分类号]
R285.5
[基金项目]
中国博士后科学基金(2023M740790);广东省重点领域研发计划项目(No.2020B1111110002);广州市青年人才托举工程项目(QT20220101283)