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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 modulates the formation of atherosclerotic plaque by activating nuclear factor of activated T cell c1 (NFATc1). Methods: Eighteen Apo E ~ (- / -) mice were randomly divided into three groups (n = 6): control group (pretreatment of lentivirus with intraperitoneal injection of 200μg ), OX40-activated group (200μg of activated OX40 antibody injected intraperitoneally after lentivirus control pretreatment) and NFATc1 group (200μg of activated OX40 antibody injected intraperitoneally after si NFATc1 lentivirus treatment) The atherosclerotic plaque model was established. The pathological changes of arterial intima were detected by HE and Masson staining. The expression of NFATc1 in atherosclerotic plaque was detected by immunohistochemistry and Western blot. Results: HE staining and Masson staining showed that carotid plaque area was increased, intimal hyperplasia was obvious and plaque collagen hyperplasia was significantly increased in the OX40-excited mice compared with the control group; carotid plaque area was significantly decreased in the NFATc1-silenced mice , The degree of intimal hyperplasia was significantly reduced, plaque collagen fibers hyperplasia weakened. Immunohistochemistry results showed that compared with the control group, the expression of NFATc1 in carotid plaques of OX40 group was significantly increased (t = 9.896, P <0.01), while the expression of NFATc1 in silencing group was significantly decreased (t = -3.167, P <0.05) . Western blotting showed that the expression of NFATc1 in carotid plaques of OX40 group was significantly higher than that of control group (t = 17.648, P <0.01), and NFATc1 expression in carotid plaque of NFATc1 group was significantly decreased compared with that of OX40 group t = -4.747, P <0.05). Conclusion: The OX40-OX40L signal regulates the formation of atherosclerotic plaques through NFATc1.