中文摘要：

目的探讨CD137-CD137L信号通路是否通过活化T细胞核因子c1（NFATc1）促进动脉粥样硬化斑块内血管新生。方法将载脂蛋白E基因敲除小鼠分为3组，即对照组、CD137刺激组和CD137抑制组，每组均为5只小鼠，采用免疫组织化学法检测小鼠主动脉斑块内的CD31含量。将小鼠内皮细胞（bend．3）分为4组，即空白对照组、IgG同型对照组、CD137刺激组和CD137抑制组，采用Western blot检测内皮细胞的NFATcl总蛋白和核蛋白水平。采用流式细胞术检测内皮细胞膜表面的CD137蛋白表达水平。采用酶联免疫吸附实验（ELISA）检测内皮细胞裂解液中的CD137蛋白水平。采用Transwell迁移实验检测内皮细胞的迁移能力。将内皮细胞分为5组，即对照组、CD137刺激组、沉默NFATc1细胞株＋CD137刺激组、CD137抑制组和过表达NFATc1细胞株＋CD137抑制组，检测各组内皮细胞的管腔形成能力。结果（1）CD137刺激组的斑块内CD31表达水平高于对照组（1191±187比115±30，P〈0．05）；CD137抑制组的斑块内CD31表达水平（450±92）低于CD137刺激组（P〈0．05）。（2）CD137刺激组内皮细胞内的NFATc1总蛋白（2．18±0．30比1．00±0．00，P〈0．05）和核蛋白（3．07±0．03比1．00±0．00，P〈0．05）水平均高于IgG同型对照组；CD137抑制组内皮细胞内的NFATc1总蛋白（0．84±0．09）和核蛋白（0．82±0．04）水平均低于CD137刺激组（P均〈0．05）。（3）流式细胞术显示，肿瘤坏死因子．d刺激后内皮细胞的CD137荧光强度高于正常内皮细胞（5163±329比1660±162，P〈0．05）。（4）ELISA显示，肿瘤坏死因子-α刺激后内皮细胞裂解液中的CD137蛋白水平高于正常内皮细胞[（573．4±23．7）pg／mg比（69．5±16．7）pg／mg，P〈0．05]。（5）CD137刺激组的内皮细胞迁移数量多于IgG同型对照组（1．19±0．13比1．00±0．00，P〈0．05）；CD137抑制组的内皮细胞迁移

英文摘要：

Objective To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells cl （NFATcl）. Methods Apolipoprotein E knock out mice were divided into the following groups： control group （n = 5）, CD137 activated group（ n = 5 ） and CD137 inhibited group （ n = 5 ）. Immunohistochemistry was performed to detect the expression of CD31 in aortic plaque. Endothelial cells （ bend. 3 ） were purchased from ATCC and divided into the following groups： control group, IgG isotype control group, CD137 activated group and CD137 inhibited group. Western blot was used to determine total protein and nucleoprotein expression of NFATcl. The expression level of CD137 protein on the surface of endothelial cells was detected by flow cytometry （FCM） and CD137 protein of lysate of endothelial cells was detected by enzyme-linked immunosorbent assay （ELISA）. Transwell assay was used to observe the migration ability of endothelial cells. Matrigel tube formation ability of endothelial cells were tested in the following groups： control group, CD137 activated group, silent NFATcl ＋ CD137 activated group, CD137 inhibited group, and over expressed NFATel ＋ CD137 inhibited group. Results （ 1 ） In vivo, the expression level of CD31 was significantly higher in the aortic plaque of CD137 activated group than in control group（ 1 191 ＋ 187 vs. 115 ± 30 ,P 〈 0. 05 ）, while which was significantly downregulated in CD137 inhibited group（450 ± 92, P 〈 0. 05）. （2） The level of nueleoprotein（3.07 ±0.03 vs. 1.00 ±0. 00,P 〈0.05） and total protein（2. 18 ± 0. 30 vs. 1.00 ±0. 00,P 〈0. 05） of NFATcl were significantly higher in CD137 activated group than in IgG isotype control group. The level of nncleoprotein（0. 82 ±0. 04） and total protein（0. 84 ± 0. 09） of NFATcl were significantly lower in CD137 inhibited group than in CD137 activated group（ both P 〈 0. 05 ）. （ 3 ） FCM results showed that th