OX40-OX40L信号通过活化T细胞核因子c1调控ApoE^(-/-)小鼠动脉粥样斑块形成  

OX40-OX40L signaling regulates the formation of atherosclerotic plaque in ApoE^(-/-) mice via NFATc1

作　　者：严洋[1] 张嘉文[1] 臧光耀 郭栋[1] 杨云稀 贺骏达 潘诵弦 许文荣[1] 严金川[2] 

机构地区：[1]江苏大学医学院临床医学系,江苏镇江212013 [2]江苏大学附属医院心内科,江苏镇江212001

出　　处：《江苏大学学报（医学版）》2017年第1期14-17,23,共5页Journal of Jiangsu University：Medicine Edition

基　　金：国家自然科学基金资助项目(81170279);江苏省六大人才高峰资助项目(WS074);江苏省333人才资助项目(BRA2014162);江苏省高校大学生创新创业计划项目(201510299043Z)

摘　　要：目的:探讨OX40-OX40L信号是否通过活化T细胞核因子c1(nuclear factor of activated T cells c1,NFATc1)调控动脉粥样硬化斑块的形成。方法:选取18只载脂蛋白基因敲除(Apo E^(-/-))小鼠,随机均分为3组(n=6):对照组(慢病毒对照预处理后腹腔注射Ig G2b 200μg)、OX40激动组(慢病毒对照预处理后腹腔注射激动型OX40抗体200μg)、沉默NFATc1组(si NFATc1慢病毒处理后腹腔注射激动型OX40抗体200μg),采用颈动脉硅胶圈快速置入法构建动脉粥样硬化斑块模型;HE及Masson染色检测动脉血管内膜病理改变;免疫组织化学和蛋白质印迹法检测动脉粥样硬化斑块内NFATc1表达。结果:HE及Masson染色结果显示,与对照组相比,OX40激动组小鼠颈动脉斑块面积增加,内膜增生明显,斑块内胶原纤维增生明显;沉默NFATc1组颈动脉斑块面积明显减少,内膜增生程度明显降低,斑块内胶原纤维增生减弱。免疫组织化学结果显示,与对照组比较,OX40激动组颈动脉斑块中NFATc1表达明显增加(t=9.896,P<0.01),而沉默NFATc1组表达明显减少(t=-3.167,P<0.05)。蛋白质印迹结果显示,OX40激动组颈动脉斑块中NFATc1表达较对照组明显增高(t=17.648,P<0.01),沉默NFATc1组颈动脉斑块中NFATc1蛋白表达量较OX40激动组表达明显减少(t=-4.747,P<0.05)。结论:OX40-OX40L信号通过NFATc1调控动脉粥样硬化斑块的形成。Objective： To investigate whether OX40-OX40L signaling regulates the formation of atherosclerotic plaque via nuclear factor of activated T cells cl （NFATcl）. Methods： Eighteen apolipoprotein gene knockout（ ApoE -/- ） mice were equally divided into three goups（ n = 6）, that is control group（ intraperitoneal injection of 200μg IgG2b after control lentiviral pretreatment） , OX40 agonist group （intraperitoneal injection of agonistic 200 μg OX40 antibody after control lentiviral pretreatment） and silencing NFATcl group （intraperitoneal injection of agonistic 200 μg OX40 antibody after siNFATel lentiviral pretreatment）. Atherosclerotic plaque model was produced by perivascular carotid collar placement in ApoE-/- mice. HE and Masson staining were used to detect the morphological change and fiber contents of the plaques. The protein level of NFATcl was detected by immunohistochemieal and Western blotting assays, respectively. Results： HE and Masson staining revealed that the area of the plaque and fibrin proliferation in OX40 ago-nist group was significantly higher than that in control group, but decreased in silencing NFATcl group. Expression level of NFATcl was significantly increased（P 〈0.01 ） in OX40 agonist group, and decreased in silencing NFATcl group, compared with control group （P 〈 0.05 ）. Conclusion： OX-40-OX40L interaction may regulate the expression of NFATcl and promote the formation of the atherosclerotic plaque.

关 键 词：OX40-OX40L 活化T细胞核因子c1 动脉粥样硬化 

分 类 号：R543.5[医药卫生—心血管疾病]