| 胰高血糖素样肽-1 受体激动剂减轻高糖诱导的巨噬细胞炎性反应的机制 |
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| 引用本文： | 邱小玲,白晓苏,李冬梅.胰高血糖素样肽-1 受体激动剂减轻高糖诱导的巨噬细胞炎性反应的机制[J].医学分子生物学杂志,2022,19(2):157-162. |
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| 作者姓名： | 邱小玲 白晓苏 李冬梅 |
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| 作者单位： | 1.深圳市龙华区人民医院内分泌科 广东省深圳市, 518109
2安康市中医医院妇科 陕西省安康市, 725000 |
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| 基金项目： | 深圳市龙华区科技创新资金项目 |
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| 摘 要： | 目的 探究胰高血糖素样肽-1 受体 (glucagon-like peptide-1 receptor, GLP-1R) 激动剂 ( exendin4) 减轻高糖诱导的巨噬细胞炎性反应的机制。 方法 小鼠单核巨噬细胞白血病细胞 (RAW264. 7) 分为 3
组分别做以下处理: 对照组 (RAW264. 7 细胞正常培养基培养)、 高糖诱导组 (RAW264. 7 细胞高葡萄糖培
养基培养)、 exendin-4 组 (RAW264. 7 细胞高葡萄糖培养基培养, 添加 exendin-4)。 通过 RT-qPCR 检测不
同处理组的 GLP-1R mRNA 水平, 以及 M1 的促炎因子一氧化氮合酶 ( nitric oxide synthase, iNOS), 白介素
( interleukin, IL) -6、 肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α) 和 M2 特异的基因 IL-10, 甘露糖受
体 1 (mannose receptor 1, MRC-1), 巨噬细胞半乳凝素 1 (macrophage galectin 1, MGL-1)、 精氨酸酶 (Arginase-1, ARG-1) 的 mRNA 水平。 通过免疫印迹 (WB) 检测 VE-钙黏着蛋白和 ZO-1, 以及细胞间粘附分
子-1 (intercellular adhesion molecule-1, ICAM-1) 和血管细胞粘附分子-1 ( vascular cell adhesion molecule-1,
VCAM-1) 的表达。 通过蛋白质印迹分析 p-STAT3 和 p-JNK 蛋白表达。 结果 与对照组相比, 高糖诱导组
的 GLP-1R mRNA 水平降低 (P< 0. 05), 与高糖诱导组相比, exendin-4 组的 GLP-1R mRNA 水平增加 (P<
0. 05)。 与对照组相比, 高糖诱导组 iNOS, IL-6 和 TNF-α 的 mRNA 水平增加, IL-10、 MRC-1、 MGL-1 和
ARG-1 的 mRNA 水平降低 (P< 0. 05), 与高糖诱导组相比, exendin-4 组 iNOS, IL-6 和 TNF-α 的 mRNA 水平
降低, IL-10、 MRC-1、 MGL-1 和 ARG-1 的 mRNA 水平增加 (P< 0. 05)。 与对照组相比, 高糖诱导组 VE-钙
黏着蛋白和 ZO-1 表达降低, ICAM-1 和 VCAM-1 表达增加 (P< 0. 05), 与高糖诱导组相比, exendin-4 组
VE-钙黏着蛋白和 ZO-1 表达增加, ICAM-1 和 VCAM-1 表达降低 (P< 0. 05)。 与对照组相比, 高糖诱导组 pSTAT3 和 p-JNK 蛋白表达增加 (P< 0. 05), 与高糖诱导组相比, exendin-4 组 p-STAT3 和 p-JNK 蛋白表达降
低 (P< 0. 05)。 结论 exendin-4 抑制磷酸化 STAT3 和磷酸化 JNK 激活, 促进 M2 极化和抑制 M1 极化, 降
低 ICAM-1 和 VCAM-1 表达, 减轻高糖诱导的巨噬细胞炎性反应。
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| 关 键 词： | 胰高血糖素样肽-1 受体 激动剂 高糖 巨噬细胞 炎症 |
Glucagon-like Peptide-1 Receptor Agonist Alleviates High Glucose-in-duced Macrophage Inflammation |
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| QIU Xiaoling,BAI Xiaosu,LI Dongmei.Glucagon-like Peptide-1 Receptor Agonist Alleviates High Glucose-in-duced Macrophage Inflammation[J].Journal of Medical Molecular Biology,2022,19(2):157-162. |
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| Authors: | QIU Xiaoling BAI Xiaosu LI Dongmei |
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| Affiliation: | 1Department of Endocrinology, People’s Hospital of Shenzhen Longhua District, Shenzhen, Guangdong, 518109, China
2Department of Gynecology, Ankang Hospital of Traditional Chinese Medicine, Ankang, Shaanxi,
725000, China |
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| Abstract: | Objective To explore the mechanism by which the glucagon-like peptide-1 receptor (GLP-1R) agonist ( exendin-4 ) reduces the inflammation and endothelial damage induced
by high glucose in macrophages. Methods Mouse monocyte macrophage leukemia cells
(RAW264. 7) were divided into groups as follows: control group (RAW264. 7 cells cultured innormal medium) ; high glucose induction group (RAW264. 7 cells cultured in high glucose medium) ; exendin-4 group ( RAW264. 7 cells cultured in high glucose medium supplemented with
exendin-4). The mRNA expression level of GLP-1R was detected by RT-qPCR. The mRNA expression levels of M1 pro-inflammatory factors nitric oxide synthase ( iNOS) , interleukin ( IL) -6,
tumor necrosis factor ( TNF) -α ( TNF-α) and M2 specific gene IL-10, mannose receptor 1
(MRC-1) , macrophage galectin 1 ( MGL-1) , arginine-1 ( ARG-1) were also detected by RTqPCR. The expression levels of VE-cadherin, ZO-1, intercellular adhesion molecule-1 ( ICAM1) and vascular cell adhesion molecule-1 (VCAM-1) were detected by Western blotting. The expression levels of p-STAT3 and p-JNK were analyzed by Western blotting. ResultsThe expression
level of GLP-1R mRNA was significantly decreased in the high glucose induced group compared
with the control group ( P < 0. 05). The expression level of GLP-1R mRNA was significantly increased (P < 0. 05) in the exendin-4 group compared with the high glucose induction group. In
the high glucose induced group relative to the control group, the expression levels of iNOS, IL-6
and TNF-α mRNA were significantly increased, and the expression levels of IL-10, MRC-1,
MGL-1 and ARG-1 mRNA were significantly decreased (P < 0. 05). These indicators were significantly improved in the exendin-4 group compared with the high glucose induced group (P < 0. 05)
. Compared with the control group, the expression levels of VE-cadherin and ZO-1 in the high glucose induced group were decreased, and the expression levels of ICAM-1 and VCAM-1 were increased (P < 0. 05 ) , which were significantly reversed in the exendin-4 group ( P < 0. 05 )
. Compared with the control group, the protein expression levels of p-STAT3 and p-JNK in the high
glucose induced group were increased ( P < 0. 05). They were significantly decreased in the exendin-4 group when compared with the high glucose induced group (P < 0. 05). Conclusion Exendin-4 can inhibit the activation of the JNK-STAT3 pathway, promote M2 polarization and inhibit
M1 polarization, reduce the expression of ICAM-1 and VCAM-1, and alleviate high glucose-induced macrophage inflammatory response. |
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| Keywords: | lucagon-like peptide-1 receptor agonist high glucose macrophages inflammation endothelial injury |
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