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目的探讨多西环素对大鼠急性心肌梗死(MI)后转化生长因子-β1(TGF-β1)表达及心肌细胞凋亡的影响。方法将30只成年Wistar大鼠随机分为假手术组、MI组及多西环素组。通过结扎冠状动脉左前降支建立大鼠MI模型。采用ELISA检测血清心肌肌钙蛋白I(c-Tn I)水平,Western blot检测心肌组织TGF-β1及caspase-3蛋白表达,末端标记法(TUNEL)检测心肌细胞凋亡。结果与假手术组比较,MI组及多西环素组c-Tn I水平升高,TGF-β1及caspase-3蛋白表达水平升高,心肌细胞凋亡指数明显增加,差异有统计学意义(P<0.05)。多西环素可降低c-Tn I水平,下调心肌组织TGF-β1及caspase-3蛋白表达,抑制心肌细胞凋亡,差异有统计学意义(P<0.05)。结论 MI后TGF-β1表达明显上调,心肌细胞凋亡增加,是心室重塑发生的重要机制。多西环素可通过下调TGF-β1表达,抑制心肌细胞凋亡,进而延缓心室重塑进程。
Objective To investigate the effect of doxycycline on the expression of transforming growth factor-β1 (TGF-β1) and cardiomyocyte apoptosis after acute myocardial infarction (MI) in rats. Methods Thirty adult Wistar rats were randomly divided into sham operation group, MI group and doxycycline group. Rat MI model was established by ligation of left anterior descending coronary artery. Serum cardiac troponin I (cTnI) levels were measured by ELISA. The expression of TGF-β1 and caspase-3 protein in myocardium was detected by Western blot. Cardiomyocyte apoptosis was detected by TUNEL. Results Compared with the sham operation group, the levels of c-Tn I and the expression of TGF-β1 and caspase-3 in MI group and doxycycline group were significantly higher than those in sham operation group P <0.05). Doxycycline reduced the level of c-Tn I, down-regulated the expression of TGF-β1 and caspase-3, and inhibited the apoptosis of cardiomyocytes. The difference was statistically significant (P <0.05). Conclusion After MI, the expression of TGF-β1 is significantly up-regulated and the apoptosis of cardiomyocytes is increased. It is an important mechanism of ventricular remodeling. Doxycycline can delay the process of ventricular remodeling by down-regulating the expression of TGF-β1 and inhibiting cardiomyocyte apoptosis.