二氢睾酮对雄性小鼠Grave病模型淋巴细胞因子的影响

目的研究5α-二氢睾酮(DHT)对雄性BALB/c小鼠Grave病模型发生发展及其脾脏淋巴细胞因子分泌的影响。方法6~8周龄雄性BALB/c小鼠按数字表法随机分为对照组、造模组、安慰剂组和DHT组4组。用腺病毒表达的人促甲状腺素受体抗体A-亚单位(human thyroid stimulating hormone receptor antibody A-subunit,Ad-TSHR289)免疫雄性BALB/c小鼠诱导建立Grave病模型,在免疫前1周DHT组皮下植入5mg DHT,安慰剂组植入安慰剂,观察DHT对小鼠甲状腺功能的影响;用流式细胞学方法检测小鼠的脾脏淋巴细胞分泌干扰素γ(IFNγ)、白细胞介素(IL)-4、IL-10、IL-9及IL-17的细胞百分比变化。结果造模组小鼠的总甲状腺素(117.76±32.69)nmol/L比(33.08±12.61)nmol/L]与游离甲状腺素(15.01±11.55)pmol/L比(3.55±1.88)pmol/L]明显高于对照组,P值均<0.0001;DHT组小鼠的甲状腺功能略低于安慰剂组,总甲状腺素(114.80±44.27)nmol/L比(123.17±77.73)nmol/L;游离甲状腺素(13.48±6.01)pmol/L比(14.19±12.65)pmol/L,但差异无统计学意义(P值均>0.05)。DHT组BALB/c小鼠脾脏分泌IL-10的2型辅助性T细胞(Th2)百分比明显高于安慰剂组(7.11±3.29)%比(3.51±1.36)%,P<0.05];DHT组小鼠脾脏分泌IFNγ、IL-4、IL-9及IL-17的细胞百分比与安慰剂组差异无统计学意义(P>0.05)。结论DHT降低雄性BALB/c小鼠Grave病模型甲状腺功能的作用不甚显著。DHT可能通过上调细胞因子IL-10而发挥对雄性BALB/c小鼠Grave病模型的免疫调节作用。

The influence of dihydrotestosterone on cytokine releases in male mice model with Graves disease

Objective To study the influences of dihydrotestosterone(DHT)on the development of experimental autoimmune Graves disease(EAGD),and to observe the effect of DHT on cytokines in male BALB/c mice model.Methods Male BALB/c mice aged 6-8 weeks were divided into 4 groups using random number table:(1)control group;(2)EAGD group;(3)placebo group;(4)DHT group.EAGD mice were induced with an adenovirus expressing the human thyroid stimulating hormone receptor antibody A-subunit(Ad-TSHR289).DHT(5mg)or a matching placebo were implanted one week before the first immunization.Thyroid hormones were detected with radioimmunoassay kit..Cytokinessuch as interferonγ(IFNγ),interleukin(IL)-4,IL-10,IL-9,and IL-17]producing cells from the spleen were detected using flow cytometry.Results As expected Ad-TSHR289 treatment increased total thyroxineEAGD group vs.control group:(117.76±32.69)nmol/L vs.(33.08±12.61)nmol/L,P<0.0001]and free thyroxineEAGD group vs.control group:(15.01±11.55)pmol/L vs.(3.55±1.88)pmol/L,P<0.0001].Treatment of DHT slightly lowered thyroid hormonesDHT group vs.placebo group:total thyroxine(114.80±44.27)nmol/L vs.(123.17±77.73)nmol/L;free thyroxine(13.48±6.01)pmol/L vs.(14.19±12.65)pmol/L],without significant difference(all P>0.05)].However,the percentage of IL-10,but not IFNγ,IL-4,IL-9 and IL-17,secreted spleen cells increased in DHT group than in the placebo group(7.11±3.29)%vs.(3.51±1.36)%,P<0.05].Conclusion The effects of DHT on thyroid hormone are mild.It might play an immunomodulatory role in the male mouse Graves disease model by up-regulating the cytokine IL-10.