Wu Hou-ke, Wang Wei, Li Hong, Bu Hong, Zhang Peng
Sichuan Da Xue Xue Bao Yi Xue Ban. 2014 May;45(3):371-5.
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.
Hyperlipidemic rats model as for the study objects firstly were established. Then the high [5 mg/(kg x d)] and low [1 mg/(kg x 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.
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).
CsA can significantly upregulate 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.
观察环孢素A(CsA)对高脂血症大鼠血管内皮细胞凝集素样氧化低密度脂蛋白(ox-LDL)受体1(LOX-1)表达的影响。
首先建立高脂血症大鼠模型作为研究对象。然后分别用高剂量[5mg/(kg·d)]和低剂量[1mg/(kg·d)]的CsA刺激这些大鼠,以血脂正常的大鼠作为对照。干预结束后,分别采用蛋白质免疫印迹法和免疫组织化学法观察胸主动脉血管内皮细胞上LOX-1和C反应蛋白(CRP)的蛋白表达情况。同时检测血清中氧化型低密度脂蛋白(ox-LDL)和活性氧(ROS)水平。
观察发现,用CsA处理的高脂血症大鼠血管内皮细胞上LOX-1表达明显上调(P<0.05),但血清中ox-LDL水平无明显变化(P>0.05)。进一步研究结果表明,CsA可增加血管内皮细胞上CRP的表达及血清中ROS水平(P<0.05)。
CsA不仅可通过ox-LDL/LOX-1途径,还可通过ROS/CRP途径显著上调高脂血症大鼠血管内皮细胞上LOX-1的表达,这可能会增加动脉粥样硬化的发生概率。