异鼠李素通过TLR4/MyD88/NF-κB通路抑制大鼠脑动脉瘤的形成

Isorhamnetin attenuates rat cerebral aneurysm formation by TLR4/MyD88/NF-κB signaling pathway

目的探讨异鼠李素(ISO)抑制大鼠脑动脉瘤(CA)的形成及其作用机制。方法选取12只7周龄SD雄性大鼠建立CA大鼠模型,并随机分为脑动脉瘤模型组(CA)以及异鼠李素组(ISO),每组6只,另取6只同龄SD雄性大鼠为假手术组(Sham)。检测各组大鼠血压和动脉瘤大小;HE染色检测大鼠脑血管组织形态;ELISA检测大鼠脑动脉血管组织的TNF-α、MCP-1、IL-6和IL-1β炎症因子水平;RT-PCR检测大鼠脑动脉血管组织中NF-κB和下游MCP-1、MMP-9 mRNA水平;Western bolt法检测TLR4/MyD88/NF-κB信号通路相关蛋白表达情况。结果ISO可以降低CA模型大鼠血压,减小动脉瘤体积,抑制TNF-α、MCP-1、IL-6和IL-1β等炎症因子的水平、下调NF-κB和下游MCP-1、MMP-9 mRNA的表达水平,抑制TLR4/MyD88/NF-κB信号通路。结论ISO通过抑制TLR4/MyD88/NF-κB信号通路减轻CA大鼠脑动脉血管组织炎症反应,抑制脑动脉瘤的形成。

Objective To study isorhamnetin(ISO)inhibit the formation of cerebral aneurysm(CA)formation in rats and the mechanisms of action.Methods Twelve 7-week-old male Sprague-Dawley rats underwent a CA induction procedure,and the rats were randomly divided into 2 groups with 6 mice in each group.Another 6 rats were set as sham operation group.The levels of blood pressure and the volume of the aneurysm in the rats were measured.Levels of TNF-α,MCP-1,IL-6 and IL-1βin rat brain blood vessels were detected by ELISA.The levels of NF-κB,MCP-1 and MMP-9mRNA in the aneurysmal walls were detected by RT-PCR.The expression of TLR4/MyD88/NF-κB signaling pathwayrelated proteins were detected by Western blot.Results ISO can reduce the blood pressure and the aneurysm size,inhibit TNF-α,MCP-1,IL-6,and IL-1βlevels,downregulate the levels of NF-κB,MCP-1 and MMP-9 mRNA and inhibit the expression of TLR4/MyD88/NF-κB signaling pathway-related proteins.Conclusion ISO attenuates inflammation via inhibiting TLR4/MyD88/NF-κB signaling pathway,which might suppress CA formation.