天津医药 ›› 2017, Vol. 45 ›› Issue (7): 682-685.doi: 10.11958/20170446

• 细胞与分子生物学 • 上一篇    下一篇

艾塞那肽对波动血糖损伤的 HRMCs 的保护作用及机制

张建双,郭婷婷,谢云   

  1. 天津医科大学代谢病医院内分泌研究所,卫生部激素与发育重点实验室, 天津市代谢性疾病重点实验室 (邮编 300070)
  • 收稿日期:2017-04-11 修回日期:2017-06-13 出版日期:2017-07-15 发布日期:2017-08-08
  • 通讯作者: 谢云 E-mail:737415120@qq.com

Protective effect and mechanism of exenatide on HRMCs injured by fluctuating hyperglycemia

ZHANG Jian-shuang,GUO Ting-ting,XIE Yun   

  1. Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China
  • Received:2017-04-11 Revised:2017-06-13 Published:2017-07-15 Online:2017-08-08

摘要: 目的 观察胰高血糖素样肽 1 (GLP-1) 受体激动剂类药物艾塞那肽对波动血糖培养下受损伤的人肾小球 系膜细胞(HRMCs)内质网应激(ERS)的影响, 并探讨其机制。方法 将体外培养的 HRMCs 分为 3 组: 对照组(N组, 5.6 mmol/L 葡萄糖培养 24 h)、 波动血糖组 (F 组, 30 mmol/L 葡萄糖培养 3 h 后 5.6 mmol/L 葡萄糖培养 2 h, 重复 3次, 5.6 mmol/L 葡萄糖培养过夜)、 波动血糖+艾塞那肽组(F+G 组, 在 F 组基础上加用 100 nmol/L 艾塞那肽)。MTT法测定各组细胞增殖能力; 流式细胞术检测细胞凋亡率; Western blot 法测定葡萄糖调节蛋白 78 (GRP78) 和 CCAAT/增强子结合蛋白同源蛋白 (CHOP) 的表达水平。结果 与 N 组相比, F 组细胞增殖能力降低, 细胞凋亡率升高, 内质网应激相关标志分子 GRP78 和 CHOP 表达水平均升高 (P<0.05); 加用艾塞那肽干预后, 与 F 组比较, F+G 组细胞增殖水平升高, 细胞凋亡率降低, 同时, GRP78 和 CHOP 表达水平均下降 (P<0.05)。结论 艾塞那肽可能通过下调内质网应激水平来减轻波动血糖对 HRMCs 的损伤。

关键词: 肾小球系膜细胞, 细胞增殖, 细胞凋亡, 内质网应激, 波动血糖, 艾塞那肽

Abstract: Objective To observe the effect of exenatide on endoplasmic reticulum stress (ERS) in human renal mesangial cells (HRMCs) injured by fluctuating hyperglycemia culture, and to explore the mechanism. Methods HRMCs were randomly divided into three groups: control group (group N, cells were cultured in 5.6 mmol/L glucose for 24 h),fluctuating hyperglycemia group (group F, cells were cultured in 30 mmol/L glucose for 3 h, 5.6 mmol/L glucose for 2 h,repeated three times in one day, then 5.6 mmol/L glucose overnight), fluctuating hyperglycemia and exenatide group (group F+G, HRMCs were cultured in fluctuating hyperglycemia and 100 nmol/L exenatide). MTT assay was used to measure the viability in each group. The apoptosis rates were detected by flow cytometry in three groups. The relative expression of glucose regulated protein78 (GRP78) and CCAAT/enhancerbinding protein homologous protein (CHOP) were tested by Western blot assay. Results Compared with the group N, the cell proliferation level decreased, the cell apoptosis rate increased, and the expression levels of GRP78 and CHOP increased in F group (P < 0.05). After treatment with exenatide,the cell proliferation rate increased, cell apoptosis rate decreased (P < 0.05), and the expression levels of GRP78 and CHOP decreased in F+G group, compared with those of the group F (P < 0.05). Conclusion Exenatide can reduce the damage of fluctuating hyperglycemia on HRMCs by down-regulating the stress levels of the endoplasmic reticulum stress.

Key words: mesangial cells, cell proliferation, apoptosis, endoplasmic reticulum stress, fluctuating hyperglycemia, exenatide

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