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作 者:李覃[1,2] 王火[3] 陈虹[2,4] 刘晓光[4] 杨金娜[4] 曹波[4] 高颖[4]
机构地区:[1]天津武警后勤学院病原生物与免疫学教研室,天津300162 [2]天津市职业与环境危害生物标志物重点实验室,天津300162 [3]天津武警后勤学院附属医院,天津300162 [4]天津武警后勤学院生药与药剂学教研室,天津300162
出 处:《中国药理学通报》2013年第2期184-189,共6页Chinese Pharmacological Bulletin
基 金:国家自然科学基金(No 81202843);中国博士后科学基金特别资助(No 201104796);天津市应用基础与前沿技术研究计划(No 11JCYBJC14600)
摘 要:目的探讨土槿乙酸(pseudolaric acid B,PB)对T细胞介导特异性免疫应答的调节作用及分子机制。方法以二硝基氟苯(2,4-Dinitrofluorobenzene,DNFB)诱导小鼠迟发型超敏反应(delayed-type hypersensitivity,DTH),局部外涂PB进行干预后检测耳肿胀度,并进一步观察PB体外作用对DTH小鼠淋巴细胞及抗原特异性T细胞增殖水平的影响,流式细胞术分析DTH小鼠CD4+CD25+Foxp3+Treg细胞数量,Western blot方法检测p38MAPK的磷酸化活性表达水平。结果 PB能够明显减轻DTH小鼠耳片厚度和重量的增加,体外作用亦能有效抑制DTH小鼠淋巴细胞以及抗原特异性T淋巴细胞增殖,其免疫抑制作用机制可能与促进Treg产生、上调p38MAPK信号通路有关。结论 PB体内外均具良好的免疫抑制活性,可通过增加Treg细胞、抑制效应细胞增殖等途径发挥作用,有望研发成为新型抗炎免疫调节剂。Aim To investigate the regulation of and molecular mechanism of pseudolaric acid B(PB) in specific immune response mediated by T lymphocytes.Methods The mouse models of delayed-type hypersensitivity(DTH) were induced by 2,4-Dinitrofluorobenzene(DNFB).Then,the ear swelling was measured after administered topically with PB.In vitro,the proliferation of lymphocytes from DTH mice and antigen-specific T lymphocytes was detected to explore the effect of PB.Besides,the percentage of CD4^+CD25^+Foxp3^+Treg cells was analyzed by flow cytometry and the phosphorylation of p38MAPK was evaluated by Western Blot assay.Results PB could inhibit the in-crease of ear thickness and ear weight in DTH mice,and suppress the proliferation of lymphocytes from DHT mice and antigen-specific T lymphocytes,whose mechanism might be involved in inducing the generation of Treg and promoting p38MAPK signalling.Conclusions PB has a favorable immunosuppressive activity both in vitro and in vivo.Meanwhile,this study provides a new rational research strategy for PB to make it ultimately become a useful anti-inflammation and immunoregulation agent.
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