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甲巯咪唑对大鼠甲状腺球蛋白诱导的自身免疫性甲状腺炎的影响。

The influence of methimazole on thyroglobulin-induced autoimmune thyroiditis in the rat.

作者信息

Rennie D P, McGregor A M, Keast D, Weetman A P, Foord S M, Dieguez C, Williams E D, Hall R

出版信息

Endocrinology. 1983 Jan;112(1):326-30. doi: 10.1210/endo-112-1-326.

Abstract

Experimental autoimmune thyroid disease was induced in August rats by immunization with rat thyroglobulin in complete Freund's adjuvant. Disease severity, assessed by thyroid histology and circulating levels of anti-TG antibody measured by an enzyme immunoassay, was maximal between 30 and 60 days after the initial immunization and thereafter waned. Thyroid function through the duration of the disease, assessed by measurement of serum TSH levels by RIA, remained normal. Once the natural history of the disease was established, groups of rats received methimazole (MMI) with or without T4 in their drinking water, either before or after disease induction. The animals were bled at regular intervals and killed on day 49 for histological grading of their thyroids. MMI alone (group 3) or with T4 (group 4) before disease induction significantly reduced the severity of the disease, although the effect on circulating antibody levels was less marked in the animals in group 4. In animals given MMI alone (group 5) or with T4 (group 6) after establishment of the disease, MMI again significantly reduced the severity of the established disease, although this effect was less marked in the T4 supplemented animals. MMI significantly impaired the induction and reduced the severity of experimental autoimmune thyroid disease in August rats. The ability of MMI to influence the autoimmune process may have important implications for the use of this and other agents that act on the immune system in the management of human autoimmune disease.

摘要

通过用完全弗氏佐剂中的大鼠甲状腺球蛋白免疫,在八月龄大鼠中诱导实验性自身免疫性甲状腺疾病。通过甲状腺组织学评估疾病严重程度,并通过酶免疫测定法测量抗甲状腺球蛋白抗体的循环水平,在初次免疫后30至60天达到最大值,此后逐渐减弱。通过放射免疫分析法测量血清促甲状腺激素水平来评估疾病持续期间的甲状腺功能,结果显示仍保持正常。一旦确定了疾病的自然病程,在疾病诱导之前或之后,给大鼠组在饮用水中添加甲巯咪唑(MMI),添加或不添加T4。定期对动物进行采血,并在第49天处死,对其甲状腺进行组织学分级。在疾病诱导前单独给予MMI(第3组)或与T4一起给予(第4组)可显著降低疾病严重程度,尽管第4组动物中对循环抗体水平的影响不太明显。在疾病确立后单独给予MMI(第5组)或与T4一起给予(第6组)的动物中,MMI再次显著降低了已确立疾病的严重程度,尽管在补充T4的动物中这种效果不太明显。MMI显著损害了八月龄大鼠实验性自身免疫性甲状腺疾病的诱导并降低了其严重程度。MMI影响自身免疫过程的能力可能对使用这种及其他作用于免疫系统的药物来治疗人类自身免疫性疾病具有重要意义。

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