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上调血红素氧合酶1对糖尿病心肌梗死大鼠心功能的远期影响 被引量:4

Long-term effects of heme oxygenase 1 overexpression on post-infarction heart function in diabetic rats
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摘要 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 clarify the impact of increased heme oxygenase-1 (HO-1) expression on cardiac function of diabetic rats with myocardial infarction and its mechanism. Methods: Sixty adult male Wistar rats were randomly divided into five groups ( n = 12) : sham oper- ation group (sham), diabetes + sham operation group (DM + sham), diabetes + MI group (DM + MI) , diabetes + myocardial infarc- tion + cobalt original porphyrin (CoPP) group (DiM + MI + CoPP), diabetes + myocardial infarction + CoPP+ tin parphyrin (SnMP) group (DM + MI + CoPP + SnMP). CoPP 4.5 mg/kg or SnMP 15 mg/kg were administered at the day next to MI operation, for six weeks, once a week. At the 28th week post operation, the echocardiography, left heart via the carotid artery indoor intubation were used to ob- serve the long-term influence of HO-1 inducer (cobalt protoparphyrin, CoPP) and activity of HO inhibitor (tin porphyrin, SnMP) on the in- dices of left ventricular remodeling and cardiac function after the intervention. Blood glucose (GLU), total cholesterol (TC), C-reactive pro- tein (CRP), sermn creatinine (Cr), aminotransferase (ALT) and other indicators were measured. ELISA was used to test interleukin-6 (IL- 6), tumor necrosis factor (TNF), nitric oxide (NO), prostacyclin (PGI2), adiponectin, and ultra sensitive CRP (HsCRP) level. Results: HO-1 inducer, CoPP, could ameliorate + dp/dtmax, left ventricular ejection fraction and left ventricular shortening fraction in diabetic my- ecardial infarction rats. It could also decrease left ventricular end-diastolic diameter. The serum bilirubin, NO and PGI2 levels, myocardial phosphorylated endothelial nitric oxide synthasee( peNOS), phosphorylated activated protein kinase( pAkt ) ,phosphorylated adenosine monophos- phate-activated protein kinase(pAMPK) expression were also significantly elevated, and the serum hs-CRP and TNF levels were significantly inhibited. Compared to inducer group, cardiac function were worse in the inhibitor group. Conclusion: Upregulated HO-1 level can improve the endothelial function, inhibite of the inflarmnatory response and enhance the antioxidant substances in serum bilirubin via peNOS-pAMPK pathway, which effectively inhibit ventricular remodeling and improve the long-term cardiac function after infarction in diabetic rats.
出处 《中国应用生理学杂志》 CAS CSCD 2014年第5期421-426,共6页 Chinese Journal of Applied Physiology
基金 北京市自然基金资助项目(7122175)
关键词 血红素氧合酶1 心肌梗死 糖尿病 心力衰竭 heme oxygenase 1 myocardial infarction diabetes heart failure
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参考文献10

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二级参考文献89

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