白藜芦醇通过促进活化T淋巴细胞凋亡改善小鼠实验性自身免疫性脑脊髓炎  

Resveratrol promotes activation-induced cell death of T lymphocytes and improves experimental autoimmune encephalomyelitis

作　　者：陈蔼如 沈燕[1] 罗琼[1] 徐强[1] CHEN Ai-ru;SHEN Yan;LUO Qiong;XU Qiang(School of Life Science,Nanjing University,State Key Laboratory of Pharmaceutical Biotechinology,Nanjing 210023,China)

机构地区：[1]南京大学生命科学学院,医药生物技术国家重点实验室,江苏南京210023

出　　处：《中国药理学通报》2022年第11期1627-1633,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No.81773743,81973331)。

摘　　要：目的探讨白藜芦醇(resveratrol,Res)促进活化T淋巴细胞凋亡发生的作用特点及机理,在此基础上观察Res对小鼠实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)的治疗效果。方法Annexin V/PI双染法考察Res对小鼠原代naive T淋巴细胞和anti-CD3/anti-CD28活化的T淋巴细胞凋亡的影响。体外在CD4^(+)T淋巴细胞和Jurkat细胞上建立活化诱导的细胞死亡模型,PI单染法或Annexin V/PI双染法考察Res促进T淋巴细胞活化诱导的细胞死亡发生的时间效应,Western blot法检测细胞内凋亡相关蛋白的变化情况。利用MOG35-55诱导小鼠实验性自身免疫性脑脊髓炎模型,观察Res治疗效果,并检测模型组和给药组小鼠CD4^(+)T淋巴细胞凋亡情况。结果Res不影响naive T细胞的存活,而促进活化T淋巴细胞的凋亡。随着Res浓度的增加,T淋巴细胞活化诱导的细胞死亡发生明显增加,凋亡相关蛋白PARP、Caspase-3的剪切增多。此外,Res可以延迟小鼠EAE发病时间,降低临床评分,减少脊髓中炎性细胞的浸润,并且给药组小鼠CD4^(+)T淋巴细胞对活化诱导的细胞死亡更加敏感。结论Res促进T淋巴细胞活化诱导的细胞死亡并能改善小鼠EAE。Aim To explore the characteristics and mechanism of resveratrol(Res)in promoting apoptosis of T lymphocytes and to investigate the therapeutic effect of Res on experimental autoimmune encephalomyelitis(EAE)in mice.Methods Annexin V/PI double staining was used to investigate the effect of Res on the apoptosis of mouse primary naive T lymphocytes and anti-CD3/anti-CD28 activated T lymphocytes.Activation-induced cell death models were established on CD4^(+)T lymphocytes and Jurkat cells in vitro,and the effect of Res on activation-induced cell death was detected by PI single staining or Annexin V/PI double staining.The expression of apoptosis related proteins were detected by Western blot.EAE model in mice was induced by MOG35-55,and the therapeutic effect of Res administration was investigated.The apoptosis of CD4^(+)T lymphocytes from vehicle group and Res group was detected.Results Res did not affect the survival of naive T cells,but promoted the apoptosis of activated T lymphocytes.With the increase of Res concentration,activation-induced cell death of CD4^(+)T cells and Jurkat cells significantly increased,and the cleavage of apoptosis related proteins PARP and Caspase-3 increased.In addition,Res delayed the onset of EAE,reduced the clinical score,and decreased the infiltration of inflammatory cells in spinal cord.The CD4^(+)T lymphocytes from the mice with Res administration were more sensitive to activation-induced cell death.Conclusion Res promotes activation-induced cell death of T lymphocytes and ameliorates EAE in mice.

关 键 词：白藜芦醇 T淋巴细胞 凋亡 活化诱导的细胞死亡 CASPASE-3 实验性自身免疫性脑脊髓炎 

分 类 号：R-332[医药卫生] R284.1R329.25R331.125R744.3