Glibenclamide ameliorates transplant-induced arteriosclerosis and inhibits macrophage migration and MCP-1 expression
Glibenclamide ameliorates transplant-induced arteriosclerosis and inhibits macrophage migration and MCP-1 expression
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格列本脲可改善移植引起的动脉硬化并抑制巨噬细胞迁移和 MCP-1 表达
DOI：
10.1016/j.lfs.2019.117141
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Xia Jiahong
中科院分区：
文献类型：
--
作者：
Zou Yanqiang;Zhou Cheng;Xu Heng;Yu Jizhang;Ye Ping;Zhang Hao;Chen Shanshan;Zhao Jing;Le Sheng;Cui Jikai;Jiang Lang;Wu Jie;Xia Jiahong
格列本脲是一种2型糖尿病药物，具有抗炎和自身免疫特性。本研究探讨了格列本脲对移植诱导的动脉硬化以及潜在的分子events.MethodsMale C57 Bl/6（H-2b）和BALB/c（H-2d）小鼠的影响，用于主动脉移植。我们使用苏木精和伊红（HE）和弹性货车吉森（EVG）染色进行组织学评估，并使用qRT-PCR和ELISA测量mRNA和蛋白质水平。分离小鼠腹腔巨噬细胞的脂多糖（LPS）刺激和格列本脲治疗，然后通过ELISA，Western blot，和Transwell assays. Results格列本脲抑制移植诱导的动脉硬化在体内。在形态学上，格列本脲减少了结缔组织中的炎性细胞积聚和胶原沉积。在基因水平，格列本脲抑制主动脉细胞因子mRNA水平，包括白细胞介素-1 β（IL-1β; 10.64 ± 3.19 vs. 23.77 ± 5.72;P< .05），肿瘤坏死因子-α（TNF-α; 4.59 ± 0.78 vs. 13.89 ± 5.42; P <0.05），单核细胞趋化蛋白-1（MCP-1; 202.66 ± 23.44 vs. 1172.73 ± 208.80;P<0.01），而格列本脲治疗2周后小鼠血清中IL-1β、TNF-α和MCP-1水平也降低（IL-1β，39.40 ± 13.56 ng/ml对78.96 ± 9.39 ng/ml;P<0.01; TNF-α，52.60 ± 13.00 ng/ml对159.73 ± 6.76 ng/ml; P <0.01; MCP-1，56.60 ± 9.07 ng/ml对223.07 ± 36.28 ng/ml; P< .001）。此外，格列本脲通过抑制核因子-κB（NF-κB）通路的活化和MCP-1的产生，抑制巨噬细胞表达和分泌炎症因子。结论格列本脲通过降低体内炎症因子，抑制巨噬细胞迁移和MCP-1的产生，对主动脉移植诱导的动脉粥样硬化具有保护作用。
AimsGlibenclamide, a diabetes mellitus type 2 medication, has anti-inflammatory and autoimmune properties. This study investigated the effects of glibenclamide on transplant-induced arteriosclerosis as well as the underlying molecular events.MethodsMale C57Bl/6 (H-2b) and BALB/c (H-2d) mice were used for aorta transplantation. We used hematoxylin and eosin (HE) and Elastic Van Gieson (EVG) staining for histological assessment, and qRT-PCR and ELISA to measure mRNA and protein levels. Mouse peritoneal macrophages were isolated for lipopolysaccharide (LPS) stimulation and glibenclamide treatment followed by ELISA, Western blot, and Transwell assays.ResultsGlibenclamide inhibited transplant-induced arteriosclerosis in vivo. Morphologically, glibenclamide reduced inflammatory cell accumulation and collagen deposition in the aortas. At the gene level, glibenclamide suppressed aortic cytokine mRNA levels, including interleukin-1β (IL-1β; 10.64 ± 3.19 vs. 23.77 ± 5.72;P< .05), tumor necrosis factor-α (TNF-α; 4.59 ± 0.78 vs. 13.89 ± 5.42; P < .05), and monocyte chemoattractant protein-1 (MCP-1; 202.66 ± 23.44 vs. 1172.73 ± 208.80;P< .01), while IL-1β, TNF-α, and MCP-1 levels were also reduced in the mouse sera two weeks after glibenclamide treatment (IL-1β, 39.40 ± 13.56 ng/ml vs. 78.96 ± 9.39 ng/ml;P< .01; TNF-α, 52.60 ± 13.00 ng/ml vs. 159.73 ± 6.76 ng/ml; P < .01; and MCP-1, 56.60 ± 9.07 ng/ml vs. 223.07 ± 36.28 ng/ml;P< .001). Furthermore, glibenclamide inhibited macrophage expression and secretion of inflammatory factors in vitro through suppressing activation of the nuclear factor-κB (NF-κB) pathway and MCP-1 production.ConclusionGlibenclamide protected against aorta transplantation-induced arteriosclerosis by reducing inflammatory factors in vivo and inhibited macrophage migration and MCP-1 production in vitro.