GLP-1对2型糖尿病合并银屑病的治疗效应及其作用机制研究

It is reported that GLP-1 analogue has a surprising effect on improving psoriasis in type 2 diabetes mellitus.In our study, The pro-psoriasis cytokines such as TNF-α and IL-17 decrease in the serum from the type 2 diabetes mellitus patients or type 2 diabetes mellitus rat model treated by GLP-1 analogue. It implies that GLP-1 may improve the psoriasis in type 2 diabetes mellitus through inhibiting systemic and local inflammation. Thus, this project is to study the effect of GLP-1 analogues liraglutide on the damage of skin in patients with type 2 diabetes mellitus accompanied by psoriasis and in animal models，then identify the role of Jak/Stat3 singnaling way in the inhibition of the GLP-1 on imflammation factors produced by Th17 cells,and demonstrate the role of involvement of TRAF2/MAPK and TRAF2/NF-kB singnaling way in the inhibition of the GLP-1 on the proliferation activity of keratinocytes in vitro and in vivio by establishing the animal model.This project will not only shed a light on understanding the mechanism of psoriasis in type 2 diabetes mellitus and new indication of Liraglutide, but also efficiently alleviate the pressure on patients physically, psychologically and economically.

研究显示，胰高血糖素样肽-1（GLP-1）类似物治疗对2型糖尿病合并银屑病患者的皮肤损害具有很好的疗效。本课题组前期研究发现，在GLP-1类似物治疗的2型糖尿病患者和大鼠中，血清和皮肤组织中肿瘤坏死因子α（TNF-α）和白细胞介素17（IL-17）等银屑病相关性炎症因子的水平降低，提示GLP-1可能通过减轻系统性和（或）局部性炎症而改善2型糖尿病合并银屑病患者的皮肤损害。因此，本项目拟在2型糖尿病合并银屑病患者和小鼠模型中，明确GLP-1类似物利拉鲁肽对皮肤损害的治疗效果；在离体和动物实验中，确定Jak/Stat3信号通路在GLP-1抑制辅助性T细胞17炎症因子产生中的作用，确定TRAF2/MAPK和TRAF2/NF-κB信号通路在GLP-1制角质形成细胞增殖和炎症因子产生中的作用。本项目将阐明GLP-1类似物治疗2型糖尿病合并银屑病的机制，并为其治疗提供理论基础和实验依据。

研究显示，胰高血糖素样肽-1（GLP-1）类似物治疗对2型糖尿病合并银屑病患者的皮肤损害具有很好的疗效。本课题组前期研究发现，在GLP-1类似物治疗的2型糖尿病患者和大鼠中，血清和皮肤组织中肿瘤坏死因子α（TNF-α）和白细胞介素17（IL-17）等银屑病相关性炎症因子的水平降低，提示GLP-1可能通过减轻系统性和（或）局部性炎症而改善2型糖尿病合并银屑病患者的皮肤损害。因此，本项目在2型糖尿病合并银屑病患者和小鼠模型中，明确了GLP-1类似物利拉鲁肽对皮肤损害的治疗效果；在离体和动物实验中，确定Jak/Stat3信号通路在GLP-1抑制辅助性T细胞17炎症因子产生中的作用，确定TRAF2/MAPK和TRAF2/NF-κB信号通路在GLP-1制角质形成细胞增殖和炎症因子产生中的作用。本项目阐明了GLP-1类似物治疗2型糖尿病合并银屑病的机制，并为其治疗提供理论基础和实验依据。