脂联素通过减轻氧化应激治疗动脉粥样硬化的研究

观察不同滴度的脂联素腺病毒载体对高脂饮食载脂蛋白E基因敲除小鼠动脉粥样硬化模型的影响，以探讨脂联素抗动脉粥样硬化（AS）是否与减轻氧化应激有关。将48只健康成年12周龄载脂蛋白E基因敲除小鼠随机分为4组，对照组，模型组，低剂量脂联素组，高剂量脂联素组。对照组给予正常饮食8周；模型组给予高脂饮食8周；低剂量脂联素组每两周经尾静脉注射脂联素腺病毒载体1．0×108p．f．u，实验期间高脂饮食；高剂量脂联素组每两周经尾静脉注射脂联素腺病毒载体5．0×108p．f．u．实验期间高脂饮食。实验结束后，摘眼球采血取血清，测定总胆固醇（TC），甘油三酯（TG），低密度脂蛋白（LDL-C），高密度脂蛋白（HDL-C），以及血清脂联素（APN）含量，超氧化物歧化酶（SOD）活性，丙二醛（，MDA）含量，取小鼠主动脉血管。实时荧光定量扩增法（RT-PCR）测定小鼠主动脉血管APN，内皮型一氧化氮合酶（eNOS）的表达。与模型组比较，外源性的脂联素降低了血清TG，TC，LDL-C，MDA的含量，血清SOD活性增加，上调动脉血管中APN和eNOS的表达。AS损伤面积明显减少，分别降低了26％和31％（P＜0．05），脂纹区的脂滴直径降低极显著（P＜0．01），随着APN剂量的增加，AS损伤逐步减轻，但是低剂量脂联素组和高剂量脂联素组的差异没有统计学意义。减轻氧化应激是脂联素抑制动脉粥样硬化的一种保护机制和途径。

Protective Effect of Adiponectin on Atherosclerosis by Relieve Oxidative Stress

To investigate the effect of different dose on atherosclerosi（AS）and oxidative stress and their dose-effect ralationship. fourty-eight healthy apolipoprotein E-deficient（apoE -/-）mice were randomly divided into four groups：control group,high-fat diet group,low and high dose of adenovirus adiponectin.12 mice for each group.The CON group were given normal chow and water.The HFD group were given high-fat diet for 8 weeks.The APN group were injected adenovirus（Ad-APN 1.0 ×108 p.f.u and 5.0 ×108 p.f.u respectly）via the tail vein every 2 weeks,last for 8 weeks.And the APN group were put on high-fat diet feeding.After animals were anesthetized,blood samples were obtained.Serum APN were measured with commercial ELISA kits.Serum superoxide dismutase （SOD）activity and malondialdehyde（MDA）was detectd by chemical chromatometry.Total cholesterol（TC）,triglyceride（TG）,high-density lipoprotein cholesterol（HDL-C）,low-density lipoprotein cholesterol（LDL-C）levels were assessed using spectrophoto-metric asssay.RT-PCR technique was used to analyze levels of mRNA expression for endothelial nitric oxide synthase （eNOS）and Adiponectin（APN）in aortic.The lesion formation in aortic sinus was measured with histochemical analyses.Compared with HFD group,The lesion formation in aortic sinus was inhibited by 26%and 31%respectively in low-APN group and high-APN group.The serum TC,TG,HDL-C,MDA levels were decreased significantly.SOD activity were increased significantly.The mRNA expression for eNOS in aortic were increased significantly.Adiponectin may protect aortic from AS injury by reducing oxidative stress.