环孢霉素A调控高脂血症大鼠血管内皮LOX-1表达的机制研究

目的观察环孢霉素A（CsA）对高脂血症大鼠血管内皮凝集素样氧化型低密度脂蛋白受体-1（LOX-1）表达的影响及其机制。方法首先建立高脂血症大鼠模型，然后分别采用高〔5 mg/（kg·d）〕、低〔1 mg/（kg·d）〕剂量的CsA对高脂血症大鼠进行灌胃7 d，正常血脂的大鼠（正常对照组）及单纯高脂血症模型组于同时点用等量生理盐水灌胃。干预结束后，分别采用Western blot、免疫组织化学方法观察大鼠胸主动脉血管内皮上LOX-1和C-反应蛋白（CRP）蛋白的表达，并采用试剂盒检测血清中氧化型低密度脂蛋白（ox-LDL）以及活性氧簇（ROS）的表达水平。结果与单纯高脂血症模型组相比，不同剂量的CsA均可上调高脂血症大鼠血管内皮细胞上LOX-1的表达（P<0.05），而对血清中ox-LDL的表达没有明显影响（P>0.05）；不同剂量组CsA均可增加高脂血症大鼠血管内皮上CRP的表达以及血清中ROS的表达水平，以高剂量组最明显（P<0.05）。结论在高脂环境中，CsA除了能通过上调ox-LDL血清水平刺激LOX-1上调外，还能通过激活CRP和ROS途径上调LOX-1的表达水平，这些因素可能促进动脉粥样硬化的发生。

英文摘要:

Objective To observe the influence of Ciclosporin A (CsA) on the expression of lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1(LOX-1) on vascular endothelium of hyperlipidemic rats. Methods Hyperlipidemic rats model as for the study objects firstly were established. Then the high 〔5 mg/（kg·d）〕 and low〔1 mg/（kg·d）〕 dose of CsA were used to stimulate these rats, while the rats of normal blood lipids as control. After the end of intervention, the protein expressions of LOX-1 and C-reactive protein (CRP) on vascular endothelium of thoracic aorta were observed by Western blot and immunohistochemistry respectively. The serum levels of ox-LDL and reactive oxygen species (ROS) were also examined. Results An obviously up-regulated expression of LOX-1 on vascular endothelium of hyperlipidemic rats treated with CsA was observed (P<0.05), but not the serum level of ox-LDL (P>0.05). The further study result implied that CsA could increase the expression of CRP on vascular endothelial cells and serum level of ROS (P<0.05). Conclusion CsA can significantly up-regulate the expression of LOX-1 on vascular endothelium of hyperlipidemic rats through not only ox-LDL/LOX-1 pathway but also ROS/CRP pathway, which could cause the probability of occurrence of atherosclerosis.

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