上海交通大学学报(医学版)

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胰岛素诱导的大鼠急性低血糖对心律失常发生及心肌connexin 43表达的影响

王光宇,叶婷婷,张庆勇   

  1. 上海交通大学附属第六人民医院心内科, 上海 200233
  • 出版日期:2015-07-28 发布日期:2015-08-27
  • 通讯作者: 张庆勇, 电子信箱: zhang_qingyong71@qq.com。
  • 作者简介:王光宇(1989—), 男, 硕士生; 电子信箱: wanggysjtj@163.com。
  • 基金资助:

    上海市科委基金(13ZR1431500)

Effects of insulin-induced acute hypoglycemia of rats on incidence of cardiac arrhythmia and expression of connexin 43

WANG Guang-yu, YE Ting-ting, ZHANG Qing-yong   

  1. Department of Cardiology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China
  • Online:2015-07-28 Published:2015-08-27
  • Supported by:

    Foundation of Science and Technology Commission of Shanghai Municipality, 13ZR1431500

摘要:

目的  研究胰岛素诱导的大鼠急性低血糖对心律失常发生及心肌缝隙连接蛋白43 (connexin 43,Cx43)表达的影响。方法  链脲佐菌素(STZ)腹腔注射制备糖尿病(DM)大鼠模型。造模成功的大鼠随机分为糖尿病高血糖组(DM组,n=9)和糖尿病低血糖组(DMHY组,n=9);同时将同一批次未建模大鼠随机分为正常血糖组(Sham组,n=9)和低血糖组(NHY组,n=9)。DMHY组和NHY组大鼠经颈静脉分别滴注胰岛素诱导低血糖。采用开胸在体电生理刺激诱发心律失常,对各组大鼠血清肾上腺素和去甲肾上腺素浓度进行测定,Western blotting检测各组大鼠心肌Cx43表达。结果  与Sham组比较,DM组大鼠血糖水平升高,体质量降低,室性心律失常的诱发率明显增高(P<0.05);NHY组大鼠心律失常诱发率明显增高,室颤阈值显著降低(P<0.05)。与DM组比较,DMHY组心律失常诱发率明显增高,室颤阈值显著降低(P<0.05)。各组心肌Cx43表达量由高到低依此为Sham组、DM组、NHY组和DMHY组,低血糖组与对应的非低血糖组之间的差异均有统计学意义(P<0.05)。与对应的非低血糖组(Sham组和DM组)比较,低血糖组(NHY组和DMHY组)大鼠血清肾上腺素和去甲肾上腺素水平显著升高(P<0.05)。结论  胰岛素诱导的急性低血糖可促进心律失常的发生,其机制可能与室颤阈值降低和心肌Cx43表达减少有关。

关键词: 低血糖, 糖尿病, 心律失常, connexin 43, 室颤阈值

Abstract:

Objective  To investigate the effects of insulin-induced acute hypoglycemia of rats on the incidence of cardiac arrhythmia and expression of myocardial connexin43 (Cx43). Methods  The model of diabetic rat (DM) was established by intraperitoneal injection with streptozotocin (STZ). After the model was successfully established, rats were randomly divided into the diabetic hyperglycemia group (DM group, n=9) and diabetic hypoglycemia group (DMHY group, n=9), while the same batch of normal rats were randomly divided into the normal blood glucose group (Sham group, n=9) and hypoglycemia group of normal rats (NHY group, n=9). Rats of the DMHY group and NHY group were transjugularly infused with insulin to induce hypoglycemia. The thorax was opened and arrhythmias was induced by programmed electrophysiological stimulation (PES). Serum epinephrine and norepinephrine concentrations were measured and expressions of myocardial Cx43 of each group were detected by the Western blotting. Results  Compared with the Sham group, the blood glucose level of the DM group significantly increased, body weight greatly decreased, and the induced rate of ventricular arrhythmias significantly increased (P<0.05). The induced rate of ventricular arrhythmias of the NHY group greatly increased and ventricular fibrillation threshold (VFT) significantly decreased (P<0.05). Compared with the DM group, the induced rate of ventricular arrhythmias of the DMHY group significantly increased and VFT greatly decreased (P<0.05). The descending order of the expression of myocardial Cx43 of each group was that of the Sham group, DM group, NHY group, and DMHY group. The differences between hypoglycemia groups and corresponding non-hypoglycemia groups were statistically significant (P<0.05). Compared with corresponding non-hypoglycemia groups (Sham group and DM group), epinephrine and norepinephrine levels of hypoglycemia groups (NHY group and DMHY group) significantly increased (P<0.05). Conclusion  Insulin-induced acute hypoglycemia contributes to the incidence of ventricular arrhythmias and the mechanism may be relevant to the decrease of VFT and myocardial Cx43 expression.

Key words: hypoglycemia, diabetic, arrhythmia, connexin 43, ventricular fibrillation threshold