基础医学与临床 ›› 2022, Vol. 42 ›› Issue (2): 208-214.doi: 10.16352/j.issn.1001-6325.2022.02.003

• 研究论文 • 上一篇    下一篇

MVBs及IL-1β在2型糖尿病大鼠血管钙化中的作用

郑杨, 魏海军, 申嘉陵, 刘润禹, 刘勇, 孙晓磊*   

  1. 西南医科大学附属医院 血管外科, 四川 泸州 646000
  • 收稿日期:2021-03-29 修回日期:2021-07-02 出版日期:2022-02-05 发布日期:2022-01-24
  • 通讯作者: * sunxiaolei_lg@163.com
  • 基金资助:
    国家自然科学基金(81270358);四川省卫计委课题重点研究项目(18ZD019);四川省科技厅课题面上项目(2018JY0400)

Role of MVBs and IL-1β in the vascular calcification of type 2 diabetic rats

ZHENG Yang, WEI Hai-jun, SHEN Jia-ling, LIU Run-yu, LIU Yong, SUN Xiao-lei*   

  1. Department of Vascular Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
  • Received:2021-03-29 Revised:2021-07-02 Online:2022-02-05 Published:2022-01-24
  • Contact: * sunxiaolei_lg@163.com

摘要: 目的 探究2型糖尿病血管钙化中基质囊泡(MVBs)的变化及MVBs、白介素-1β(IL-1β)在糖尿病血管钙化中的作用。方法 建立2型糖尿病大鼠钙化模型和体外细胞高糖钙化模型;用PET/CT成像、Von Kossa 染色或茜素红染色检测钙的沉积;免疫荧光染色、实时定量PCR或Western blot检测骨形态发生蛋白2(BMP-2)、核心结合因子2(RUNX 2)、MVBs标志物annexin-Ⅵ及IL-1β的表达。结果 与对照组相比,2型糖尿病大鼠主动脉或高糖钙化细胞中有明显钙沉积,且BMP-2、RUNX 2的表达显著升高(P<0.01,P<0.05);同时,annexin-Ⅵ和IL-1β的表达也明显上调(P<0.01,P<0.05),且存在共定位;用雷帕霉素诱导细胞自噬后,RUNX 2、annexin-Ⅵ和IL-1β的表达均降低(P<0.01);而用氯喹抑制自噬后,RUNX 2的表达轻微上调,而annexin-Ⅵ高表达(P<0.01)。结论 自噬通过减少MVBs的释放,并降低炎性因子IL-1β的表达,从而减轻2型糖尿病主动脉钙化。

关键词: 2型糖尿病, 血管钙化, 基质囊泡, 白介素-1β

Abstract: Objective To study the role of matrix vesicles bodies (MVBs) and interleukin-1β (IL-1β) in the vascular calcification of type 2 diabetic rats. Methods In vivo and in vitro vascular calcification models were developed by streptozotocin (STZ) plus vitamin D3 in rats with high-fat diet and β-glycerophosphate and high-glucose medium in vascular smooth muscle cells (VSMCs), respectively. Calcium deposition was detected by PET/CT, Von Kossa staining or alizarin red S staining. The expression of runt-related transcription factor 2 (RUNX 2), annexin-Ⅵ and IL-1β were detected by immunofluorescence staining, real-time quantitative PCR or Western blot. Results The aortic artery of calcified rats and the in vitro VSMCs both showed obvious calcium deposits. Compared to the control group, the expressions of bone morphogenetic protein-2 (BMP-2) and RUNX 2 significantly increased in the calcification group (P<0.01, P<0.05). At the same time, the expression of annexin-Ⅵ and IL-1β was also significantly up-regulated (P<0.01, P<0.05) and there was a co-localization between them. Rapamycin reduced expression of RUNX-2, annexin-Ⅵ and IL-1β in the calcification group (P<0.01). After the treatment of chloroquine, the expression of RUNX 2 weas slightly up-regulated and annexin-Ⅵ was high-expressed(P<0.01). Conclusions Autophagy reduces the release of MVBs and the expression of inflammatory factor IL-1β and so thereby reduces aortic calcification in type 2 diabetic rats.

Key words: type 2 diabetes mellitus, vascular calcification, matrix vesicles bodies, interleukin-1β

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