上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

内质网应激在高血糖致微血管损伤过程中的作用

王恒1，王宏英1，李继斌2，章誉尧1，彭川1，肖晓秋1   

  1. 1.重庆医科大学附属第一医院糖脂代谢实验室， 重庆 400016； 2.重庆医科大学 公共卫生与管理学院营养与食品卫生学教研室， 重庆 400016
  • 出版日期:2016-03-28 发布日期:2017-06-02
  • 通讯作者: 肖晓秋, 电子信箱: xiaoxq@cqmu.edu.cn。
  • 作者简介:王恒（1985—）， 女， 硕士生; 电子信箱: hengyv663@163.com。
  • 基金资助:

    国家自然科学基金（81270947）

Role of endoplasmic reticulum stress in hyperglycemiacaused microvascular injury

Wang Heng1, Wang Hong-ying1, Li Ji-bin2, Zhang Yu-yao1, Peng Chuan1, Xiao Xiao-qiu1   

  1. 1.Laboratory of Lipid & Glucose Metabolism, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; 2.Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China

  • Online:2016-03-28 Published:2017-06-02
  • Supported by:

    National Natural Science Foundation of China, 81270947

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摘要：

目的 探讨内质网应激在高血糖SD大鼠微血管损伤过程中的作用。方法 健康雄性SD大鼠通过腹腔注射链脲佐菌素（STZ）建立高血糖动物模型。造模成功后1个月以无创尾动脉血压测定法检测血压，期间监测大鼠体质量和随机血糖。RT-PCR测定大鼠肠系膜阻力血管中内质网应激相关因子的基因转录水平；Western blotting测定GRP78/Bip、eNOS、Akt及IRS1的蛋白质表达水平。结果 高血糖组随机血糖较对照组显著升高，收缩压、舒张压和平均动脉压也都显著高于对照组。RT-PCR结果显示,高血糖组大鼠微血管组织内质网应激主要标志物的mRNA水平均显著升高（P<0.05）。Western blotting结果显示，高血糖组Bip的蛋白表达水平显著升高（P<0.05），IRS1、Akt及eNOS的磷酸化水平均显著下降（P<0.05）。结论 持续性高血糖能诱发实验大鼠血压升高，该作用可能与内质网应激介导的微血管功能损伤、血管组织胰岛素信号通路受损，以及eNOS的活性降低有关。

关键词: 高血糖, 内质网应激, 胰岛素受体信号通路, 血管损伤

Abstract:

Objective To investigate the role of endoplasmic reticulum (ER) stress in microvascular injury in hyperglycemic SD rats. Methods Healthy male SD rats were intraperitoneally injected with streptozotocin (STZ) to construct a hyperglycemic rat model. Blood pressure (BP) was measured by noninvasive caudal artery blood pressure measurement one month after the model was constructed, and body weight and random blood glucose level were monitored. Gene transcriptional levels of ER stress-related factors in rat mesenteric resistant arteries (MRAs) were measured by RT-PCR. Protein levels of GRP78/Bip, eNOS, Akt and IRS1 were detected by Western blotting. Results Random blood glucose level, systolic BP, diastolic BP and mean arterial pressure in the hyperglycemic group were significantly higher compared with the control group. RT-PCR showed that mRNA levels of ER stress main markers in rat microvascular tissue in the hyperglycemic group significantly increased (P<0.05). Western blotting showed that Bip protein level in the hyperglycemic group significantly increased (P<0.05) and phosphorylation of IRS1, Akt and eNOS significantly decreased (P<0.05). Conclusion Persistent hyperglycemia can induce hypertension in rats, which may be associated with ER stress-mediated microvessel dysfunction, impaired insulin signaling pathway in vascular tissue and decrease in eNOS activity.

Key words: hyperglycemia, endoplasmic reticulum stress, insulin receptor signaling pathway, microvascular dysfunction