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目的:研究上调血红素氧合酶1(HO-1)的表达对糖尿病心肌梗死大鼠心功能的影响及其机制。方法:将60只成年Wistar雄性大鼠随机分为5组(n=12),分别为假手术组、糖尿病组、模型组、诱导剂组、抑制剂组。心梗造模后次日开始给药,1次/周,持续6周,术后28周,应用心脏超声、经颈动脉左心室内插管术等方法观察HO-1诱导剂钴原卟啉(CoPP)及HO活性抑制剂锡中卟啉(SnMP)干预后对心室重构及心功能各项指标的远期影响;测定血糖(GLU)、总胆红素(TB)、C反应蛋白(CRP)、血清肌酐(Cr)、转氨酶(ALT)等指标;采用ELISA测定白介素-6(IL-6)、肿瘤坏死因子(TNF)、一氧化氮(NO)、前列环素(PGI2)、脂联素、超敏CRP(HsCRP)等水平。结果:应用CoPP上调HO-1水平,能够改善糖尿病心梗大鼠左心室压力最大变化速率、左室射血分数、左室短轴缩短率,缩小左室舒张末期内径,升高血清胆红素、一氧化氮和前列环素水平,提高心肌组织磷酸化的内皮型一氧化氮合酶(peNOS)、磷酸化的活化蛋白激酶(pAkt)、磷酸化的腺苷活化的蛋白激酶(pAMPK)的表达,降低血清TNF-α、hs-CRP水平。使用SnMP后,能够阻断CoPP的上述作用。结论:上调HO-1通过peNOS、pAMPK途径能够长期地改善血管内皮功能,抑制炎症反应,提升血清胆红素等,有效抑制心室重塑,改善梗死后糖尿病大鼠远期的心功能。
Objective: To investigate the effect of heme oxygenase 1 (HO-1) on cardiac function in diabetic rats with myocardial infarction and its mechanism. Methods: Sixty adult Wistar male rats were randomly divided into 5 groups (n = 12), sham-operated group, diabetic group, model group, induction group and inhibitor group. Myocardial infarction model made administration the next day, once / week for 6 weeks, after 28 weeks, the application of cardiac ultrasound, left ventricular catheterization of carotid artery and other methods HO-1 inducer cobalt protoporphyrin (CoPP) and HO activity inhibitor tin mesoporphyrin (SnMP) on the ventricular remodeling and long-term cardiac function indicators of the long-term impact; determination of blood glucose (GLU), total bilirubin (TB), C reactive protein (CRP), serum creatinine (Cr), and aminotransferase (ALT) were detected by ELISA. The levels of IL-6, TNF, Dipyridamole, hypersensitivity CRP (HsCRP) and other levels. Results: Up-regulation of HO-1 by CoPP could improve the maximal rate of change of left ventricular pressure, left ventricular ejection fraction, shortening of left ventricular shortening, decrease of left ventricular end-diastolic diameter and elevation of serum bilirubin in diabetic rats , Nitric oxide and prostacyclin levels, increased myocardial tissue phosphorylation of endothelial nitric oxide synthase (peNOS), phosphorylated activated protein kinase (pAkt), phosphorylated adenosine-activated protein kinase (pAMPK) Expression, reduce serum TNF-α, hs-CRP levels. The use of SnMP blocked the above effects of CoPP. CONCLUSION: Up-regulation of HO-1 by peNOS and pAMPK can improve vascular endothelial function, inhibit inflammatory reaction, increase serum bilirubin and so on, effectively inhibit ventricular remodeling and improve long-term cardiac function in infarcted diabetic rats.