摘要
本研究应用咪喹莫特(imiquimod,IMQ)诱导银屑病小鼠模型,考察雷公藤甲素衍生物LB-1对IMQ诱导银屑病样炎症的影响、组织病理改变,并初步探讨LB-1应用于防治银屑病的免疫机制。结果显示,与模型组相比,LB-1显著抑制小鼠银屑病样炎症,银屑病样皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分明显降低;4 mg·kg^(-1) LB-1能够减轻IMQ诱发的小鼠脾脏肿大;2 mg·kg^(-1) LB-1能够抑制脾CD8^+(P<0.01)T淋巴细胞百分比,上调CD4^+/CD8^+T淋巴细胞比值(P<0.01),4 mg·kg^(-1) LB-1上调脾CD3^+T(P<0.01)和CD4^+T(P<0.05)淋巴细胞的百分比。基于上述实验结果,本文发现雷公藤甲素衍生物LB-1能够抑制IMQ诱导的小鼠银屑病样炎症,其免疫调节机制可能与改变脾脏中CD4^+T、CD8^+T细胞的百分比构成有关。本研究为今后LB-1及其他以雷公藤甲素为主要活性成分的雷公藤制剂在银屑病的临床应用上提供指导意义。
The aim of present study was to explore the effect of triptolide derivative LB-1 on imiquimod（IMQ）induced psoriasiform inflammation in BALB/c mice,and to investigate the immune mechanism of LB-1 in the prevention and treatment of psoriasis.In the present study,topical application of IMQ for seven days induced the psoriasiform inflammation in BALB/c mice.This is a promising mouse model of psoriasis for the natural immune reaction compared to those induced by xenograft,trangenic or gene knockout.psoriasis area and severity index（PASI）score,hematoxylin-eosin（HE）staining and flowcytometry were employed to investigate the changes of psoriasiform inflammation,histopathological response and percentage of T cells,respectively.The result showed that LB-1 significantly attenuated the psoriasiform inflammation.Compared with model group,PASI score were decreased in the LB-1 group.In the isolated immunocytes of spleen,LB-1 decreased percentage of CD8~＋（P〈0.01）T cells and increased the ratio of CD4~＋/CD8~＋T cells at the dosage of 2 mg·kg^（-1）（P〈0.01）,whereas LB-1 raised percentage of CD4~＋T cells and CD3~＋T cells at the dosage of 4 mg·kg^（-1）.In conclusion,the present study demonstrated that LB-1 attenuated psoriasiform inflammation induced by imiquimod in BALB/c mice.The mechanism of LB-1 action may be related to change percentage of CD4~＋T,CD8~＋T cells in the spleen.These results provide a basis for LB-1 or other triptolide derivative in the intervention of psoriasis in the future.
出处
《药学学报》
CAS
CSCD
北大核心
2017年第11期1692-1697,共6页
Acta Pharmaceutica Sinica
基金
北京市神经外科研究所创新基金资助项目(所青年-2016-002)
