OX40-OX40L信号对ApoE^(-/-)小鼠颈动脉斑块中亲环素A表达的影响  

Effect of OX40-OX40L Signal on the Expression of Cyclophilin A in Atherosclerotic Plaque of ApoE^(-/-) Mice

作　　者：伍超[1] 严金川[1] 逯朝阳 徐丽华[1] 王中群[1] 袁伟[1] 

机构地区：[1]江苏大学附属医院心内科,江苏省镇江市212001

出　　处：《中国动脉硬化杂志》2014年第5期443-447,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(81170279;81370409);江苏省自然科学基金及创新团队基金(BK2011486;LJ201116);江苏省六大人才高峰项目(WS-074);镇江市心血管病重点实验室项目(SS2012002)

摘　　要：目的观察OX40-OX40L信号对载脂蛋白E基因敲除(ApoE-/-)小鼠颈动脉粥样硬化斑块内亲环素A(CyPA)表达的影响。方法采用颈动脉硅胶圈植入法快速诱导ApoE-/-小鼠动脉粥样硬化斑块形成,48只雄性ApoE-/-小鼠随机分成抑制组、刺激组、对照组,刺激组腹腔注射鼠抗OX40 200μg,抑制组腹腔注射鼠抗OX40L200μg,对照组腹腔注射IgG2b 200μg,均每周一次,连续6周。分别采用免疫组织化学、Western blot和qRT-PCR检测小鼠颈动脉斑块内CyPA蛋白和mRNA的表达。结果 ApoE-/-小鼠颈动脉置管并6周高脂饮食后,对照组可见斑块形成,部分内膜和中膜增厚,弹力板变形,刺激组颈动脉斑块面积与对照组相比显著增加,而抑制组颈动脉斑块面积明显减少。与对照组相比,刺激组颈动脉斑块内CyPA蛋白和mRNA表达明显增强,而抑制组颈动脉斑块内CyPA蛋白和mRNA表达明显减弱。结论 OX40-OX40L信号能调控ApoE-/-小鼠颈动脉斑块中CyPA的表达。Aim To investigate effect of OX40-OX40L signal on the expression of cyclophilin A （CyPA） in ath- erosclerotic plaque of apolipoprotein E gene knockout （ ApoE -/- ） mice. Methods Atherosclerotic plaque model was produced by perivascular carotid collar placement in ApoE -/- mice. 48 male ApoE -/- mice were anesthetized by intrap- eritoneal injection of ketamine. Subsequently, the right common carotid artery was separated, and Silicone Collar was placed on the right common carotid artery. ApoE -/- mice were randomly allocated to inhibition group （ intraperitoneal in- jection of anti-OX40L 200 I^g, once a week, 6 weeks）, stimulation group （intraperitoneal injection of anti-OX40 200 I^g, once a week, 6 weeks） and control group （intraperitoneal injection of IgG2b 200 I^g, once a week, 6 weeks）, mice were sacrificed after high fat diet and intraperitoneal injection of antibodies was received for 6 weeks. The expression of CyPA protein and mRNA levels in atherosclerotic plaque were detected by immunohistochemisty, Western blot, qRT-PCR, re- spectively. Results Dealing with perivascular carotid collar placement and high fat diet in ApoE -/- mice after 6 weeks, plaque formation, part of intima and media thickening and elastic lamina deformation were detected in control. Compared with control group, the carotid sections of plaque area of stimulation group were significantly increased, while those in inhibition group were significantly decreased, the expressions of CyPA protein and mRNA were significantly in- creased in atherosclerotic plaque （P 〈 0. 05）. However, after intraperitoneal injection of anti-OX40L to inhibit OX40- OX40L ligand, the expressions of CyPA protein and mRNA were significantly decreased in atherosclerotic plaque （P 〈 0. 05）. Conclusion The expression of CyPA in ApoE -/- mice is modulated by the OX40-OX40L signal.

关 键 词：OX40-OX40L信号 载脂蛋白E基因敲除小鼠 亲环素A 动脉粥样硬化 

分 类 号：R363[医药卫生—病理学]