基础医学与临床 ›› 2019, Vol. 39 ›› Issue (2): 170-174.

• 研究论文 • 上一篇    下一篇

血红素加氧酶-1减轻糖尿病小鼠心肌损伤

刘守珠1,王海源2,司立宁3,王嵘4   

  1. 1. 青海红十字医院检验科
    2. 青海红十字医院
    3. 青海大学
    4. 青海大学医学院
  • 收稿日期:2018-03-01 修回日期:2018-06-19 出版日期:2019-02-05 发布日期:2019-01-16
  • 通讯作者: 王嵘 E-mail:qhwr2007@163.com
  • 基金资助:
    国家自然科学资助项目;青海省科技厅资助项目

Heme oxygenase-1 alleviates the cardiomyopathy in diabetic mice

  • Received:2018-03-01 Revised:2018-06-19 Online:2019-02-05 Published:2019-01-16

摘要: 目的 观察血红素加氧酶-1(HO-1)对链脲佐菌素(STZ)诱导的糖尿病心肌病是否发挥保护作用并探讨相关的分子机制。方法 常规腹腔注射STZ构建HO-1转基因小鼠(HO-1/DM)和同笼阴性小鼠(Wt/DM)糖尿病模型,8周后超声心动图检测小鼠左室心脏功能。HE染色检测左室心肌,用RT-qPCR法检测心肌IL-6、TNF-α、Gpx3和p47 phox mRNA的表达。给予H9C2细胞高糖培养,过表达HO-1观察其对ROS生成的影响。 结果 Wt/DM组和HO-1/DM组小鼠较Wt/Con组血糖、进食量、饮水量和尿量均明显升高,体质量显著降低。与Wt/Con组小鼠相比,Wt/DM组小鼠左室心脏功能明显障碍,HO-1/DM组小鼠左心脏功能明显好于Wt/DM组小鼠; Wt/DM组小鼠心肌结构紊乱,炎性反应细胞浸润,HO-1/DM组小鼠心肌结构趋于正常。Wt/DM组小鼠心肌中IL-6、TNF-α、Gpx3、p47phox mRNA表达较Wt/Con组小鼠升高(p<0.05),过表达HO-1可明显抑制该现象。结论 HO-1可能通过抗氧化和抗炎作用保护高血糖引起的心脏功能障碍和心肌结构损伤。

关键词: 糖尿病心肌病, HO-1, 氧化应激, 炎症

Abstract: Objective To determine whether heme oxygenase-1 (HO-1) plays a major role in modulating diabetic cardiomyopathy (DCM) and the mechanisms involved in this process. Methods: HO-1 transgenic mice (HO-1 / DM) and wild type mice (Wt / DM) diabetes model were established by conventional intraperitoneal injection of streptozotocin. After eight weeks, echocardiography was used to detect left ventricular function in mice. Left ventricular myocardium was detected by HE staining and the expression of IL-6, TNF-α, Gpx3 and p47 phox mRNA were detected by RT-qPCR. H9C2 cells were cultured in high glucose and were overexpressed HO-1 to observe its effect on ROS production. Results: Compared with Wt/Con mice, the blood glucose, food intake, water intake and urine output were significantly increased and the body weight was significantly decreased in Wt/DM and HO-1/DM mice. Compared with Wt/Con mice left ventricular function was significantly impaired in Wt/DM mice. Left ventricular function was better in HO-1/DM mice than in Wt/DM mice. Wt/DM mice myocardial structure disorder and inflammatory reaction cell infiltration. Compared with Wt/DM mice myocardial structure tends to be normal in HO-1/DM mice. In the Wt/DM mice, the expression of IL-6, TNF-α, Gpx3 and p47phox were higher than the Wt/Con mice (p<0.05), overexpression of HO-1 significantly inhibited this phenomenon. Conclusion: This study demonstrates that HO-1 is cardioprotective in the context of diabetic cardiomyopathy.

Key words: diabetes cardiomyocyte, heme oxygenase-1, oxidative stress, inflammation