胰岛素抵抗下脂蛋白相关磷脂酶A2介导的炎症因子的表达与动脉硬化关系

目的探讨胰岛素抵抗(IR)下动脉粥样硬化早期动脉内皮细胞炎症发生的机制。方法雄性Wistar大鼠20只,随机分成对照组、高脂高糖组,喂养8周后,用高胰岛素-正血糖钳夹技术测定稳态时葡萄糖输注率(GIR)来评价IR;以酶联免疫吸附方法测定血清胰岛素、血脂、C反应蛋白(CRP)以及脂蛋白相关磷脂酶A2(LP-PLA2);以免疫组织化学方法半定量测定动脉内皮细胞内核因子(NF)-κB和细胞间黏附因子(ICAM)-1的含量。结果对照组CRP和LP-PLA2低于高脂高糖组(P<0.05);对照组GIR高于高脂高糖组(P<0.05);高脂高糖组大鼠动脉内皮细胞内NF-κBI、CAM-1表达增高(P<0.05)。GIR与ICAM-1呈负相关(P<0.05)。结论长期高脂高糖饮食可导致机体发生IR。在内皮细胞受损时LP-PLA2分泌增加,并与低密度脂蛋白胆固醇结合后发生氧化,促进CRP,NF-κB激活,使ICAM-1浓度增加,从而引起动脉内皮炎症发生,最终导致不可逆的动脉粥样硬化的发生。

The relationship between inflammation factors and atherosclerosis mediated by lipoprotein related phospholipid A2 under insulin resistance

Objective Exploring the inflammation mechanism of arterial endothelial cells when early atherosclerosis happens under insulin resistance.Methods Divide 20 male Wistar rats into control group and high fat and glucose group;After 8 weeks′ feeding,evaluate steady-state glucose infusion rate(GIR)using Hyperinsulinemic-Euglycemic Clamp technique,detect serum insulin,lipid,tumor necrosis factor-α,CRP and lipoprotein related phospholipid A2(LP-PLA2)by enzyme linked immunosorbent assay;detect arterial endothelial cells nuclear factor kB(NF-κB)in arterial endothelial cells and intercellular adhesion factor-1(ICAM-1) semi-quantitatively by immunohistochemical method.Results CRP and LP-PLA2 of control group are lower than that in high fat and glucose group(P<0.05),well,GIR is higher than that in high fat and glucose group(P<0.05).The express of NF-κB and ICAM-1 in arterial endothelial cells of high fat and glucose group increase(P<0.05).GIR is Negatively correlated with ICAM-1(P<0.05).Conclusion long time high fat and glucose diet can lead to the IR.Lipid gathering is the initial power of artherosclerosis,during which process,inflammation and oxidative stress all play important roles.Secretion of LP-PLA2 increases when the arterial endothelial cell is damaged,and it can be oxidated when it is combined with Low density lipoprotein cholesterol,promoting the activation of TNF-α and CRP,increasing the concentration of ICAM-1,then giving rise to the happening of arterial endothelial inflammation,finally leading to the irreversible atherosclerosis.