外源性硫化氢对小鼠动脉粥样硬化的调节作用及机制

摘要

目的 研究外源性硫化氢(H2S)通过Toll样受体4(TLR4)对ApoE-/-小鼠动脉粥样硬化的调控作用及机制. 方法 制作ApoE-/-小鼠颈动脉粥样硬化不稳定斑块模型,外源性H2 S缓释剂GYY4137干预. 模型分为正常对照组?不稳定斑块组?不稳定斑块组+不同剂量GYY4137组?不稳定斑块+LY294002组. 检测小鼠血脂水平,油红染色检测粥样硬化斑块,ELISA法检测血浆炎症因子TNF-α?IL-6?IL-1和IL-10,Western blot检测斑块组织内TLR4?PI3K?Akt?磷酸化Akt(P-Akt)蛋白表达. 结果 与对照组比较,模型组脂质成分及促炎因子TNF-α?IL-6?IL-1增加,抑炎因子IL-10减少,粥样斑块内TLR4?PI3K?P-Akt蛋白表达增加(P<0.01).GYY4137中?高剂量干预减少模型组脂质成分及促炎因子TNF-α?IL-6?IL-1表达,增加抑炎因子IL-10,减少TLR4?PI3K?P-Akt蛋白表达(P<0.01).LY294002干预效果与GYY4137类似. 结论 外源性H2 S能调控TLR4及TNF-α?IL-6?IL-1?IL-10表达,防止ApoE-/-小鼠颈动脉粥样斑块发生?发展,作用与PI3K-Akt信号通路有关.%Objective To investigate the regulation and mechanism of exogenous hydrogen sulfide(H2S) on atherosclerosis in ApoE -/-mice by Toll-like receptor 4(TLR4).Methods The carotid artery atherosclerotic plaques in ApoE -/-mice model was established;the mice were fed with a high-fat diet and administered GYY4137 for 8 weeks.Lipid and atherosclerotic lesions were measured by oil red O staining.TNF-α, IL-6, IL-1 and IL-10 were detected by ELISA.Protein expression of TLR4, PI3K, Akt, P-Akt were evaluated by Western blot .Results Compared with the control group , the lipid composition and proinflammatory factors TNF -α, IL-6 and IL -1 increased in the model group, and the inhibitory factor IL-10 decreased, and the expression of TLR4, PI3K and P-Akt protein increased in atherosclerotic plaques (P<0.01).GYY4137 medium and high dose intervention reduced the lipid composition and proinflammatory factors TNF -α, IL-6, IL -1 expression in the model group , increased the inhibitory factor IL -10, decreased the expression of TLR 4, PI3K and P-Akt protein ( P<0.01).The effect of LY294002 intervention was similar to that of GYY4137.Conclusion Exogenous H2 S can regulate the expression of TLR 4 and TNF-α, IL-6, IL-1 and IL -10, and prevent the development of carotid atherosclerotic plaques in ApoE -/-mice, which is related to the PI3K-Akt signaling pathway .