杂色曲霉素对小鼠胸腺和脾脏转录因子Foxp3^+调节性T淋巴细胞的影响  

Effect of sterigmatocystin on transcription factor Foxp3^+ regulatory T lymphocytes of thymus and spleen in mice

作　　者：刘亚玲[1] 邢欣[1] 邢凌霄[1] 姚志刚[1] 王娟[1] 严霞[1] 王俊灵[1] 张祥宏[1] 

机构地区：[1]河北医科大学病理学研究室,河北石家庄050017

出　　处：《中国药理学与毒理学杂志》2009年第3期188-194,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：河北省自然科学基金资助项目(C2007000819);教育部科学技术研究重点资助项目(205021);河北省科技攻关研究重点资助项目(07276102D)~~

摘　　要：目的探讨杂色曲霉素(ST)对机体免疫调节功能的影响。方法BALB/c小鼠随机分为正常对照组、溶剂对照组、ST3,30,300和3000μg·kg-1组。小鼠ip给药24h后,处死取胸腺和脾脏,采用流式细胞术测定胸腺和脾脏细胞中CD4+和CD8+T淋巴细胞及转录因子Foxp3阳性(Foxp3+)调节性T淋巴细胞的百分率,免疫组织化学法检测胸腺和脾脏组织中Foxp3+调节性T淋巴细胞数量,Western蛋白印迹法和RT-PCR分别测定胸腺和脾脏组织中Foxp3蛋白和mRNA的表达。结果溶剂对照组与正常对照组比较,小鼠胸腺和脾脏CD4+,CD8+和Foxp3+T淋巴细胞百分率均无明显差异。与溶剂对照组比较,ST3μg·kg-1组胸腺CD8+T淋巴细胞百分率降低,ST3和30μg·kg-1组脾脏CD4+和CD8+T淋巴细胞百分率明显升高,ST300和3000μg·kg-1组胸腺和脾脏CD4+和CD8+T淋巴细胞百分率无明显变化。在ST3～3000μg·kg-1内,胸腺和脾脏细胞中Foxp3+调节性T淋巴细胞百分率、胸腺和脾脏组织内Foxp3+调节性T淋巴细胞数量、Foxp3蛋白和mRNA表达均随ST浓度的增高而增加。结论ST可诱导小鼠淋巴器官内Foxp3+调节性T淋巴细胞数量增加,从而影响机体免疫耐受功能。AIM To explore putative effects of sterigmatocystin （ ST ） on immunoregulatory function. METHODS BALB/c mice were randomly divided into normal control, solvent control and ST 3, 30, 300 and 3000 μg· kg-1 groups. The mice were sacrificed 24 h after ST was ip given and thymus and spleen were taken out. The percentages of CD4 ＋ and CD8 ＋ as well as transcription factor Foxp3 ＋ regulatory T lymphocytes in thymus and spleen were deter- mined with flow cytometric （FCM） method. The changes in number of Foxp3 ＋ regulatory T cells were measured with immunohistochemical staining. Foxp3 expression at protein and mRNA level in thymus and spleen were respec- tively analyzed with Western blotting and re- verse transcription polymerase chain reaction （RT-PCR） methods. RESULTS FCM re- suits showed that there were no significant differences in the percentages of CD4 ＋ , CD8 ＋ and Foxp3 ＋ T in thymus and spleen between normal control and solvent control groups. Compared with control groups, the percentage of thymus CD8 ＋ T cell in ST 3 μg· kg-1 group was significantly decreased, while that of splen ic CD4 ＋ and CD8 ＋ T cells in both ST 3 and 30 μg· kg-1 groups were all significantly in- creased. No significant differences in the percentages of CD4 ＋ or CD8 ＋ T cells were found between ST 300 and 3000 μg· kg-1 groups with control groups in thymus and spleen. At the same time, the results revealed that from 3 to 3000μg· kg-1, ST could significantly increase precentages and numbers of Foxp3 ＋ T lympho- cytes as well as expression of Foxp3 at both protein and mRNA levels in thymus and spleen dose-effectively. CONCLUSION ST expo- sure could induce increase in Foxp3 ＋ regulatory T lymphocytes in lymphatic organ, thus may af- fect the immune tolerance of host.

关 键 词：杂色曲霉素 T淋巴细胞 调节性 转录因子 胸腺 脾脏 

分 类 号：R379[医药卫生—病原生物学]