TSP1缺失可降低巨噬细胞的迁移和相关炎症表型

Thrombospondin 1 deficiency reduces the migration of macrophages and related inflammatory phenotypes

通过构建肥胖小鼠模型,探讨血小板反应蛋白1(thrombospondin 1,TSP1)在与肥胖相关的炎症反应中的作用及机制。用高脂食物喂养TSP1-/-的雄鼠和同源的WT雄鼠16周,收集血液并提取腹腔巨噬细胞,检测血浆MCP-1的水平;利用real-time PCR技术检测腹腔巨噬细胞内炎症因子IL-6、TNF-α、MCP-1和PAI-1的表达量;进一步采用Transwell技术分析巨噬细胞的迁移和黏附能力。得出以下结果:1.Real-time PCR结果显示,TSP1-/-小鼠巨噬细胞内IL-6、TNF-α、MCP-1和PAI-1mRNA表达量下降;2.Transwell结果显示,TSP1-/-小鼠的巨噬细胞向TSP1迁移的能力降低;3.WT和TSP1-/-小鼠血浆和脂肪组织中MCP-1表达均无明显差异。因此可认为,TSP1可以调节脂肪组织中巨噬细胞功能和炎症因子表达,其机制可能是通过减少炎症反应和降低巨噬细胞迁移能力实现的。

We investigated the effect and mechanism of thrombospondin 1（TSP1）in obesity-associated inflammation by an obesity mouse model.Male TSP1-/-mice and wild type littermate controls were fed with a high-fat（HF）diet for 16 weeks.Then blood was collected and peritoneal macrophages were extracted and plasma MCP-1levels were detected.Real-time PCR was used to measure the expression levels of IL-6,TNF-α,MCP-1and PAI-1.The Transwell assay was used to analyze migration and adhesion ability of macrophages.The results were：1.Real-time PCR results showed that the mRNA expression levels of IL-6,TNF-α,MCP-1and PAI-1were decreased in macrophages in TSP1-/-mice.2.Transwell assay showed that the ability of macrophages to migrate toward purified TSP1 was significantly slowed.3.There was no difference in MCP-1level in either plasma or adipose tissues between WT and TSP1-/-mice.In conclusion,TSP1 can participate in the inflammatory response by regulating the expression of inflammatory cytokines and the ability of macrophage migration.