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目的:探讨丹皮酚(paeonol,Pae)对急性心肌梗死模型大鼠心肌病理改变及转化生长因子-β_1(TGF-β_1),胶原蛋白Ⅲ(CollagenⅢ)表达的影响。方法:SPF级雄性SD大鼠,采用左冠状前降支(LAD)结扎法制作在体大鼠急性心肌梗死模型,记录结扎前及结扎后10,20,40,60,120 min,24 h心电图变化,测量各个时点ST段的偏移幅度并进行统计学分析,将造模成功后的大鼠随机分为模型组、丹皮酚低、中、高剂量组、卡托普利组;另有只穿线不结扎的假手术组,共6组,丹皮酚低、中、高剂量组分别给予ip 8.0,12.0,16.0 mg·kg~(-1)剂量的丹皮酚注射液,假手术组与模型组每天ip等体积生理盐水,卡托普利组用蒸馏水稀释其片剂碾成的药粉,给予ig 10.0 mg·kg~(-1),所有干预均1次/d;28 d后取材,HE染色观察心肌组织病理生理学改变情况,采用免疫组织化学法检测左室梗死区TGF-β_1和CollagenⅢ蛋白的表达。结果:HE染色结果显示:与假手术组比较,模型组大鼠左室病理生理学改变显著,梗死灶边缘部分心肌细胞发生肥大、伸长,左心室壁部分心肌凝固性坏死,凋亡细胞胞核固缩、胞质伊红深染,另有部分组织发生疏松水肿,与模型组比较,各治疗组大鼠心肌细胞病理改变均不同程度减轻;免疫组织化学染色结果显示:模型组与假手术组比较,TGF-β_1及collagenⅢ蛋白的表达明显增多(P<0.01);治疗组各组及卡托普利组与模型组比较,TGF-β_1及collagenⅢ蛋白表达均降低(P<0.01,P<0.05)。结论:丹皮酚可降低心肌梗死大鼠心肌的病变程度,改善心室重构及心功能,其作用机制可能是通过降低心肌组织中TGF-β_1及collagenⅢ的表达来实现的。
Objective: To investigate the effect of paeonol on myocardial pathological changes and the expression of transforming growth factor-β 1 (TGF-β 1) and collagen Ⅲ in rats with acute myocardial infarction (AMI). Methods: SPF male Sprague-Dawley (SD) male Sprague-Dawley rats were used to establish the model of acute myocardial infarction (AMI) in vivo in rats by ligating left anterior descending coronary artery (LAD). The changes of ECG before and 10, 20, 40, 60, 120, The amplitude of ST segment deviation at each time point was measured and statistically analyzed. The rats after successful modeling were randomly divided into model group, paeonol low, medium and high dose groups, and captopril group. There were 6 sham-operation groups with sham-operation group and sham-operated group with 8.0, 8.0 and 16.0 mg · kg -1 doses of paeonol, The rats in the model group were treated with equal volume of normal saline ip every day. The captopril group was diluted with distilled water to ig 10.0 mg · kg -1. All the interventions were given once / d. After 28 days, The changes of myocardial histopathology were observed by HE staining. The expressions of TGF-β 1 and Collagen Ⅲ protein in left ventricular infarction area were detected by immunohistochemistry. Results: The results of HE staining showed that the pathophysiology of left ventricle changed significantly in the model group compared with the sham-operation group, hypertrophy and elongation of myocardial cells in the marginal part of the infarct area, partial coagulation necrosis of the left ventricular wall, Systolic and contractile, cytoplasm eosin staining, and other parts of the organization loose edema, compared with the model group, the pathological changes of rat myocardial cells in each treatment group were reduced to varying degrees; immunohistochemical staining results showed: model group and sham operation group (P <0.01). Compared with the model group, the expression of TGF-β 1 and collagen Ⅲ protein in the treatment group and the captopril group were significantly decreased (P <0.01, P <0.05) ). Conclusion: Paeonol can reduce the degree of myocardial infarction in rats and improve ventricular remodeling and cardiac function. The possible mechanism is that paeonol can reduce the expression of TGF-β 1 and collagen Ⅲ in myocardium.