利拉鲁肽通过circ-sirt1/NF-κB信号通路抑制血管平滑肌细胞炎症的机制研究

doi:10.3969/j.issn.1007-3205.2022.09.002

河北医科大学学报 ›› 2022, Vol. 43 ›› Issue (9): 996-1001.doi: 10.3969/j.issn.1007-3205.2022.09.002

利拉鲁肽通过circ-sirt1/NF-κB信号通路抑制血管平滑肌细胞炎症的机制研究

河北医科大学第二医院心脏大血管外科，河北石家庄 050000

出版日期:2022-09-25 发布日期:2022-10-02
作者简介:刘钰(1984-)，男，河北石家庄人，河北医科大学第二医院副主任医师，医学博士，从事心血管外科疾病诊治研究。
基金资助:
河北省自然科学基金资助项目（H2021206062）；河北省医学科学研究课题计划（20211356）；河北医科大学第二医院科学研究基金资助项目（2h2019035）

Mechanism of lilarutide inhibiting inflammation of vascular smooth muscle cells via circ-sirt1/NF-κB signaling pathway

Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

Online:2022-09-25 Published:2022-10-02

摘要/Abstract

摘要： 目的探究利拉鲁肽(liraglutide，LIR)对肿瘤坏死因子α(tumour necrosis factor-α,TNF-α）诱导的血管平滑肌细胞炎症反应的作用及其可能的分子机制。
方法实验分为空白对照组(NC组)、TNF-α组(10 μg/L)和TNF-α+LIR组(10 μg/L TNF-α+100 nmol/L LIR)。酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测细胞培养基中的白细胞介素1β(interleukin-1β,IL-1β)和白细胞介素6(interleukin-6,IL-6)。实时荧光定量核酸扩增检测系统(real-time quantitative polymerase chain reaction detecting system,qPCR)检测circ-sirt1及细胞间黏附分子1(inter-cellular adhesion molecule 1,ICAM-1)、单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)、抑制性卡巴蛋白α(inhibitor kppa B-α，IκB-α）mRNA的表达。Western Blot检测细胞ICAM-1、MCP-1和IκB-α蛋白表达。免疫荧光检测核因子κB（nuclear factor kappa-B，NF-κB）p65蛋白分布。
结果与NC组相比，TNF-α组细胞培养基中的IL-1β和IL-6含量显著升高，ICAM-1、MCP-1 mRNA及蛋白表达显著升高，IκB-α mRNA及蛋白表达显著减低，circ-sirt1表达显著降低，NF-κB p65蛋白主要定位在细胞核。与TNF-α组相比，TNF-α+LIR组IL-1β和IL-6含量显著减少，ICAM-1、MCP-1蛋白表达显著降低，IκB-α蛋白表达显著增加，circ-sirt1表达显著升高，NF-κB p65蛋白细胞核定位减少。
结论利拉鲁肽能够抑制血管平滑肌细胞的炎性反应，可能是通过抑制炎症介质释放及circ-sirt1/NF-κB信号通路的激活发挥作用。

关键词: 利拉鲁肽, 肌细胞, 平滑肌, NF-κB

Abstract: ObjectiveTo investigate the effect of liraglutide(LIR) on tumor necrosis factor(TNF)-α-induced vascular smooth muscle cell inflammation and its possible molecular mechanism.
MethodsThe experiment was divided into three groups: blank control group(NC group), TNF-α group(10 μg/L) and TNF-α +LIR group(10 μg/L TNF-α + 100 nmol/L LIR). IL-1β and IL-6 in cell culture medium were detected by enzyme linked-immunosorbent assay(ELISA). The mRNA expressions of ICAM-1, MCP-1 and IκB-α and circ-sirt1 were detected by real-time quantitative polymerase chain reaction detecting system（qPCR）. The protein expressions of ICAM-1, MCP-1 and IκB-α were detected by Western blot. The protein distribution of NF-κB p65 was detected by immunofluorescence.
ResultsCompared with NC group, the levels of IL-1β and IL-6 in TNF-α group were significantly increased, and the mRNA and protein expressions of ICAM-1 and MCP-1 were significantly increased. The mRNA and protein expression of IκB-α was significantly decreased, and the expression of circ-sirt1 was significantly decreased. NF-κB p65 protein was mainly localized in the nucleus. Compared with TNF-α group, the levels of IL-1β and IL-6 and the protein expressions of ICAM-1 and MCP-1 were significantly decreased, while the protein expression of IκB-α was significantly increased in TNF-α+LIR group. Meanwhile，the expression of circ-sirt1 was significantly increased and nuclear localization of NF-κB p65 protein was decreased in TNF-α+LIR group.
ConclusionLilarutide can inhibit the inflammatory response of vascular smooth muscle cells, possibly by inhibiting the release of inflammatory mediators and the activation of circ-sirt1/NF-κB signaling pathway.

Key words: liraglutide, myocytes, smooth muscle, NF-κB ,

刘钰, 王星, 崔红占, 孙涌泉, 步纪强, 陈子英. 利拉鲁肽通过circ-sirt1/NF-κB信号通路抑制血管平滑肌细胞炎症的机制研究 [J]. 河北医科大学学报, 2022, 43(9): 996-1001.

LIU Yu, WANG Xing, CUI Hong-zhan, SUN Yong-quan, BU Ji-qiang, CHEN Zi-ying. Mechanism of lilarutide inhibiting inflammation of vascular smooth muscle cells via circ-sirt1/NF-κB signaling pathway [J]. Journal of Hebei Medical University, 2022, 43(9): 996-1001.

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利拉鲁肽通过circ-sirt1/NF-κB信号通路抑制血管平滑肌细胞炎症的机制研究

Mechanism of lilarutide inhibiting inflammation of vascular smooth muscle cells via circ-sirt1/NF-κB signaling pathway

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