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

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（TNE）、一氧化氮（NO）、前列环素（PG12）、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。

Long-term effects of heme oxygenase 1 overexpression on post-infarction heart function in diabetic rats

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. Comp