乙酰胆碱受体抗体抑制烟碱对大鼠下丘脑-垂体-肾上腺轴作用的研究

目的研究乙酰胆碱受体抗体(nAchRab)IgG在烟碱模拟应激状态下对下丘脑-垂体-肾上腺 (HPA)轴各层面活动的影响,探讨重症肌无力(MG)和MG危象发生机制与HPA内分泌轴变化的关系。方法将 nAchRab IgG或正常人IgG注入大鼠侧脑室,继后经烟碱刺激;应用原位杂交、放射免疫和化学发光免疫法观察:实验组和对照组鼠下丘脑、海马和颞叶促肾上腺皮质释放激素(CRH)mRNA表达和血浆促肾上腺皮质激素(ACTH) 及皮质酮(CORT)浓度。结果在基础状态,nAchRab抑制下丘脑CRHmRNA表达,对海马、颞叶CRHmRNA表达无抑制,对血浆ACTH及CORT水平无影响;nAchRab抑制烟碱所诱导的下丘脑、海马及颞叶CRHmRNA表达,血浆 ACTH及CORT水平下降。结论 nAchRab能与下丘脑、海马及颞叶的乙酰胆碱受体(nAchR)结合,基础状态仅抑制下丘脑CRHmRNA表达;在烟碱诱导的状态下则整个HPA功能受抑制,结果模拟了应激状态MG发病和MG危象时的状况,提示MG发病和MG危象发生可能与HPA功能低下有关。

Analysis the inhibitive effects of nAchRab on hypothalamus - pituitary - adrenal axis in rat under stimulation of nicotine

Objective To study the effects of intraventricular injection of AchRab on hypolhalamus-pituitary-adrenal axis ( HPA) in rat under stress with nicotine and to investigate the change of HPA activation . Methods nAchRab-positive JgG or healthy person's IgG was injected into lateral ventriculus of rat for 3 consecutive days . Then nicotine was injected in-traperitoneally . The expression levels of CRH messenger ribonucleic acid (mRNA) in hypothalamus and limbic system and the levels of adrenocorticotropic hormone ( ACTH) and corticosterone ( CORT) in plasma were observed and quantitatively analysed by in situ hybridization and radioimmunoassay and chemical iuniinescence Immune assay in both experimental and control groups. Results In basal state the nAchRab can only inhibit the expression of CRHmRNA in hypothalamus but not in limbic system . It also can not inhibit the ACTH and CORT. The nAchRab significantly inhibited the nicotine induced the expression of CRHmRNA in hypothalamus and limbic system and plasma ACTH and CORT levels . Conclusions The results indicated that there is immunological cross reactivity between nAchRab and the neuronal nAchR in hypothalamus and limbic system . nAchRab can inhibit the expression of CRHmRNA in hypothalamus in basal state and inhibit the nicotine induced the HPA axis activation . Moreover , these findings suggests that nAchRab inhibited the HPA activation may have relation with MG and crisis of MG .