【作者】 郭小芹；

【导师】 王金龙；

【作者基本信息】 天津医科大学 ， 免疫学， 2003， 硕士

【摘要】 临床观察和实验研究指出，许多自身免疫性疾病的发病率存在明显的性别差异，女性比男性有较高的发病率，自身免疫性甲状腺疾病中的桥本氏甲状腺炎，其发病率的男女之比为1∶4-1∶19，许多学者认为女性激素特别是雌激素对自身免疫性疾病的发病有着重要的影响。为了观察雌激素和泌乳素水平变化对自身免疫性甲状腺炎发病的影响，为临床诊断和治疗提供一定的实验室依据。本课题是将切除双侧卵巢(OVX)的Wistar大鼠，用同种属SD大鼠甲状腺球蛋白(Tg)诱发实验性自身免疫性甲状腺炎(EAT)。观察大鼠甲状腺病理学改变和血清中Tg自身抗体、雌二醇水平，并采用RT-PCR检测甲状腺组织中IFN-γ和IL-10mRNA表达水平。实验结果表明，诱发为EAT实验组的大鼠血清中Tg自身抗体水平明显高于未诱发EAT的正常对照组。而卵巢切除大鼠诱发为EAT的实验组，甲状腺组织的炎性细胞浸润程度明显低于未切除卵巢大鼠诱发为EAT实验对照组，血清中雌二醇和泌乳素(PRL)水平也明显低下，甲状腺组织中IFN-γmRNA表达水平下降，而IL-10mRNA的表达水平则上升。 可以认为，大鼠切除卵巢导致血清中雌二醇和泌乳素(PRL)水平低下，会使其EAT的发病率和甲状腺的炎症反应明显地减少或缓解，又与甲状腺组织中Th2细胞因子IL-10mRNA的表达水平上升明显相关。但考虑卵巢切除致血清中雌二醇和泌乳素水平均呈低下状态，缓解和影响EAT的自身免疫应天津医科大学硕士研究生学位论文答作用，是雌二醉，抑是泌乳素的影响，还是两者的共同作用，及泌乳素的影响机制。为此，本课题又进行了澳隐亭对泌乳素的干预实验，进一步研究了泌乳素对EAT诱发的影响，并采用RT一PCR检测脾脏中IL-饥L一ZRmRNA的表达水平，探讨泌乳素的作用机制。实验结果显示，经澳隐亭干预，大鼠血清中PRL水平低下，其EAT的发病率和甲状腺组织的炎症反应也均明显减少或减轻，脾脏中IL，2/IL一ZRmRNA的表达水平较未经澳隐亭干预组降低。因此考虑单一的PRL因素也会影响EAT的发病，其机理是PRL可提高IL一2八L一ZRmRNA的表达水平，IL一2八L一ZR的相互结合刺激细胞免疫和体液免疫，增加自身免疫应答程度。可以认为泌乳素也是自身免疫性甲状腺炎发病机制中的重要因素。 结论:雌激素和泌乳素是女性体内的两种重要的内分泌激素，它们不仅有其各自内分泌的生理学意义，同时还参与机体的免疫系统调节和细胞因子的表达，直接影响自身免疫性甲状腺炎的发病率和炎症反应程度.这两种激素的作用或协同作用，也是女性在自身免疫性疾病中有较高发病率的重要因素。更多还原

【Abstract】 Many observations proposed that there is a significant gender differences inthe incidence of autoimmune diseases, furthermore, a disproportionate number is women. The predominance of autoimmune diseases among women suggests that the lelve of sex hormone, especially estrogen, may modulate susceptibility. Autoimmune thyroid diseases also have the gender gap. In human chronic (Hashimoto’s) thyroiditis, the female to male ratio is 4:1-19:1. Estradiol-17p(E2-17p) and prolactin(PRL) are two important hormones in female. To elucidate the role of estrogen in the pathogenesis of autoimmune thyroid diseases, we observed and studied the effect of the two hormones on the modulation of immune responses Such studies may have implications for clinical medicine. In this study, ten-week old ovariectomized(OVX) female rats were induced experimental autoimmune thyroiditis(EAT) by immunization with thyroglobulin(Tg) from SD rats in the presence of complete Freund’s adjuvant(CFA). Thyroiditis was pathologically evaluated by HE staining. The level of E2-17B and PRL were measured by RIA; anti-Tg antibody was detected by ELISA and IFN-r, IL-10 mRNA in thyroid gland were assayed by RT-PCR. The results suggested that high liter of anti-Tg was presented in the EAT groups, while the OVX group showed a significant reduction in the thyroid pathology and incidence of EAT. Meanwhile, the level of E2-170 and PRL were much lower in OVX rats than that in intact rats followed by the decrease in IFN-y mRNA and the increase in IL-10 mRNA.As a result of the decrease in serum levels of estradiol-17(J and prolactin, it was proposed that the balance of IFN-y and IL-10 was necessary for the induction of EAT. Whereas, OVX resulted in the consistent decreased production of the two hormones, so it was questioned whether prolactin had direct function on EAT or coordinated with E2-170. In Part two, through the intervene of PRL production by bromocriptine(BRC), we further studied the effect of prolactin on the induction of EAT. The results indicated that the incidence and severity of EAT were much lower in the group treated with BRC than in the group without treatment by BRC BRC inhibiting secretions of prolactin in the pituitary, decreased the expression level of IL-2/IL-2R mRNA in spleen. Prolactin stimulating the expression of IL-2/IL-2R mRNA, exerts a direct stimulatory effect on the immune response thereby, the enhancement of cell and humoral-based immunity will play an important function on the induction of EAT.Conclusion: As two important hormones in female, estrogen and prolactin have a reciprocal endocrinologic relationship and both hormones participate the modulation of immune system and expression of many cytokines. As a result, they play important roles on the induction of EAT. Further investigation into actions and interactions of estrogen and prolactin with autoimmunity will provide a better understanding of the female preponderance of autoimmunity and facilitate a more rational approach to hormonal immunotherapy.更多还原