IL-35在2型糖尿病合并颈动脉粥样硬化病变中的作用

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摘要目的: 探讨IL35在2型糖尿病（T2DM）合并颈动脉粥样硬化（carotid atherosclerosis，CAS）病变中的作用。方法: 选取70例T2DM患者，其中单纯T2DM 36例，T2DM合并CAS 34例，同时选择年龄、体重指数（BMI）、性别匹配的健康人群35例作为对照组。实时定量PCR检测人外周血单个核细胞（PBMCs）P35 mRNA和EBI3 mRNA表达水平；通过液相芯片仪检测各组患者血清IL35及可溶性血管细胞黏附分子1（sVCAM1）浓度。体外建立高糖刺激人脐静脉内皮细胞（HUVECs）模型，设低糖处理组（5 mmol/L葡萄糖）、高糖处理组（25 mmol/L葡萄糖）、甘露醇组（25 mmol/L甘露醇）、IL35+高糖组(50 ng/mL IL35+25 mmol/L葡萄糖)，流式细胞仪检测各组HUVECs凋亡率和VCAM1阳性率。结果：与对照组\[9.37（3.72~14.55）ng/mL\]相比，单纯T2DM组\[5.01（2.37~9.87）ng/mL\]和T2DM合并CAS组\[3.92（2.15~6.36）ng/mL\]患者血清IL35浓度明显降低，且T2DM合并CAS组降低更明显（P<0.05）；与对照组\[687.4（664.2~832.6）\]相比，单纯T2DM组\[785.2（754.5~938.1）\]及T2DM合并CAS患者\[932.4（892.6~1 028.3）\]血清sVCAM1浓度明显升高，且T2DM合并CAS患者sVCAM1浓度升高更显著。与对照组相比，单纯T2DM组和T2DM合并CAS组外周血PBMCs 中P35 mRNA表达明显下降（P<0.05）。体外培养HUVECs后，高糖组刺激24 h及48 h后HUVECs凋亡率比低糖组明显增加（P<0.05），IL35+高糖组刺激48 h后HUVECs凋亡率比高糖组明显降低（P<0.05）；高糖组刺激48 h后HUVECs VCAM1阳性率比低糖组明显升高（P<0.05），IL35+高糖组HUVECs VCAM1阳性率比高糖组明显下降（P<0.05）。结论：体内外实验证实IL35在高血糖相关的内皮细胞损伤中可能发挥保护作用。

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关键词 ： 2型糖尿病, 白细胞介素-35, 动脉粥样硬化, 血管细胞黏附分子1

Abstract：Objective: To investigate the role of IL35 in the pathogenesis of type 2 diabetes mellitus (T2DM) with carotid atherosclerosis (CAS). Methods: A total of 70 patients with T2DM were enrolled，including 36 patients diagnosed with T2DM without CAS, 34 patients diagnosed with T2DM with CAS, and 35 age, gender and body mass index(BMI) matched healthy control group were enrolled. The expression of P35 mRNA and EBI3 mRNA in peripheral blood mononuclear cells(PBMCs) were detected by realtime quantitative PCR. The concentration of serum IL35 and sVCAM1 were measured using multifunction flow type dot matrix instrument Luminex 200. The model of high glucose stimulated human umbilical vein endothelial cells (HUVECs) was established in vitro, then divided into low glucose(LG) conditions(5 mmol/L glucose), high glucose(HG) conditions (25 mmol/L glucose), high mannitol conditions(25 mmol/L mannitol) and IL35+HG (50 ng/mL IL35+25 mmol/L glucose). The apoptosis rate of HUVECs and the positive rate of VCAM1 in each group were detected by Flow cytometry. Results: Compared to those of control group \[(9.37(3.72-14.55 ng/mL)\], the concentration of serum IL35 were lower in the T2DM alone group\[5.01（2.37-9.87）ng/mL\], and much lower in T2DM with CAS group\[3.92(2.15-6.36)ng/mL\] . Compared to those of control group \[687.4（664.2-832.6）\], the concentration of serum sVCAM1 were higher in the simple T2DM group\[785.2（754.5-938.1）\], and much higher in T2DM with CAS group\[932.4（892.6-1 028.3）\]. Compared to those of control group, the expression of P35 mRNA were lower in the T2DM alone group and T2DM with CAS group. the expression of EBI3 mRNA were similar in all three groups (P>0.05). Compared to those of LG group, The apoptosis rate of HUVECs in HG group were higher after treated with 24 h and 48 h (P<0.05). Compared to those of HG group, the apoptosis rate of HUVECs were lower in IL-35+HG group after treated with 48 h. Compared with LG group, the positive rate of VCAM-1 increased in HG group after 48 h (P<0.05). Compared with HG group, the positive rate of VCAM-1 decreased in IL-35+HG group after 48 h (P<0.05). Conclusion: IL-35 may play a protective role in hyperglycemia-induced endothelial cell injury in vivo and in vitro.

收稿日期: 2018-04-24

基金资助:南京医科大学江苏康达医药卫生科研项目(2017NJMUKD022)

通讯作者: 刘娟利(通讯作者)，E-mail：18961911898@163.com

作者简介: 朱静和(1980—)，男，主治医师，硕士，主要从事糖尿病血管并发症研究；

引用本文:

朱静和1，徐昌辉1，钱雷2，刘青员1，蒋凤1，于建秀2，刘娟利2. IL-35在2型糖尿病合并颈动脉粥样硬化病变中的作用[J]. 江苏大学学报:医学版, 2018, 28(05): 431-436. ZHU Jing-he1, XU Chang-hui1, QIAN Lei2, LIU Qing-yuan1, JIANG Feng1, YU Jian-xiu2, LIU Juan-li2. The role of IL-35 in type 2 diabetes mellitus with carotid atherosclerosis . Journal of Jiangsu University(Medicine Edition), 2018, 28(05): 431-436.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2018/V28/I05/431

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