[1]杨晓晓 王峰 罗善顺 石立力.利拉鲁肽对糖尿病合并动脉粥样硬化模型中骨保护素的影响及机制研究[J].心血管病学进展,2022,(8):753-758.[doi:10.16806/j.cnki.issn.1004-3934.2022.08.021]
 YANG Xiaoxiao,WANG Feng,LUO Shanshun,et al.The effect and Mechanism of Liraglutide on Osteoprotegerin?n Diabetic Atherosclerosis Rat[J].Advances in Cardiovascular Diseases,2022,(8):753-758.[doi:10.16806/j.cnki.issn.1004-3934.2022.08.021]
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利拉鲁肽对糖尿病合并动脉粥样硬化模型中骨保护素的影响及机制研究(/HTML)
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2022年8期
页码:
753-758
栏目:
论著
出版日期:
2022-08-25

文章信息/Info

Title:
The effect and Mechanism of Liraglutide on Osteoprotegerin?n Diabetic Atherosclerosis Rat
作者:
杨晓晓 王峰 罗善顺 石立力
(哈尔滨医科大学附属第一医院干部一病房,黑龙江 哈尔滨 150001)
Author(s):
YANG Xiaoxiao WANG Feng LUO Shanshun SHI Lili
?The First Cadre Ward, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China)
关键词:
糖尿病动脉粥样硬化 血管平滑肌细胞骨保护素利拉鲁肽
Keywords:
Diabetes mellitus Atherosclerosis Vascular smooth muscle cells Osteoprotegerin Liraglutide
DOI:
10.16806/j.cnki.issn.1004-3934.2022.08.021
摘要:
目的 研究利拉鲁肽(LIRA)对糖尿病(DM)合并动脉粥样硬化(AS)模型中骨保护素(OPG)的影响,以期探讨LIRA抗AS的病理生理学机制。方法 体外研究,取SD大鼠胸主动脉,体外原代培养血管平滑肌细胞(VSMC s),给予VSMCs不同的干预,分为对照组、高糖组(HG组)、LIRA组、HG+LIRA组、HG+ERK1/2拮抗剂(PD98059)组、HG+PD98059+LIRA组、HG+GLP-1受体拮抗剂[Exe(9-39)]+LIRA组。采用Western Blot法进行OPG表达检测。体内研究中,将实验大鼠分成四组即正常对照组、LIRA组、DM+AS组、DM+AS+LIRA组。并于DM成模的0月、4月将各组的大鼠处死,留取胸主动脉进行相关检测。采用Western Blot法对胸主动脉中OPG的表达进行检测。并通过免疫组化检测各组胸主动脉在不同时间OPG的表达。结果 体外研究结果显示, 与对照组比较,HG组OPG表达显著增加。在高糖基础上给予LIRA干预后,OPG表达下降。在高糖基础上给予ERK1/2拮抗剂后,OPG表达同样下降。并且与HG+LIRA组比较,高糖+ERK1/2拮抗剂+LIRA进一步使OPG的表达水平下降。高糖+LIRA基础上给予GLP-1受体拮抗剂,可抑制LIRA对VSMCs中OPG的影响。在体内研究中,DM成模0月时,Western Blot检测各组胸主动脉OPG表达无差异。DM成模4月时,与对照组比较,DM+AS组胸主动脉OPG表达显著增高。与DM+AS组比较,DM+AS+LIRA组胸主动脉OPG表达下降。并且在DM+AS组,与0月比较,4月时胸主动脉OPG表达水平升高。使用免疫组化检测OPG表达趋势与Western Blot检测的趋势相同。结论 高糖促进VSMCs中OPG表达增加,LIRA可以减少高糖状态下OPG的表达,并且这种作用可能与ERK1/2信号通路以及GLP-1受体信号通路密切相关。
Abstract:
Objective To study the effect of liraglutide (LIRA) on osteoprotegerin (OPG) in diabetic atherosclerosis (DM+AS) rat model and explore the underlying antiatherosclerotic mechanism. Methods In vitro the thoracic aortas of SD rats were cut off. The primary vascular smooth muscle cells (VSMCs) were divided into control, high glucose (HG), LIRA, HG+LIRA, HG+PD98059 (a ERK1/2 antagonist), HG+LIRA+PD98059, and HG+LIRA+Exe (9-39) (a GLP-1 receptor antagonist) group s. OPG expression was analyzed by Western blot. In vivo rats were divided into Control, LIRA, DM+AS, and DM+AS+LIRA groups. The rats in each group were sacrificed at 0 (M0) and 4 months (M4) after the model was established, and the thoracic aorta was retained for relevant detections. OPG expressions in thoracic aorta were detected by Western Blot and immunohistochemistry. Results Compared with control group, OPG expression was significantly increased in HG group, and decreased both in HG+LIRA and HG+PD98059 groups. Compared with HG+LIRA group, OPG was further reduced in HG+PD98059+LIRA group. The effect of LIRA on OPG expressions in HG was inhibited by Exe (9-39). In vivo, there was no difference in OPG expressions at M0. Yet at M4, OPG expression in DM+AS group was significantly higher than that of control group. OPG expression in DM+AS+LIRA group was decreased than that of DM+AS group. In DM+AS group, OPG was increased at M4 compared with M0. The trend of OPG expression from immunohistochemistry was parralled with that from Western Blot. Conclusion High glucose promotes the expression of OPG in VSMCs. Liraglutide reduces OPG expressions in high glucose, which may be closely related to ERK1/2 signaling pathway and GLP-1 receptor signaling pathway.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金(81900760)
通信作者:石立力,E-mail:501338@qq.com
收稿日期:2022-02-25
更新日期/Last Update: 2022-10-08