余增才,陈洁君,麦颖琦,吴丽玉,郭秋平
YU Zengcai,CHEN Jiejun,MAI Yingqi,WU Liyu,GUO Qiuping

• 1:广州医药研究总院有限公司药物非临床评价研究中心

摘要(Abstract)：

目的在GLP实验室条件下通过组织病理学检查和免疫组织化学方法观察连续7 d给予激素类药物后,正常SD大鼠下丘脑-垂体-肾上腺轴的变化情况,在本中心建立下丘脑-垂体-肾上腺轴的病理检查方法及糖皮质激素受体在下丘脑-垂体-肾上腺轴的表达检测技术方法。方法选用SD大鼠32只,雌雄各半,将动物分为阴性对照组、激素类药物组。激素类药物组给予地塞米松磷酸钠注射液,阴性对照组给予5%的葡萄糖溶液。给药结束后,取下丘脑、垂体、肾上腺,肉眼观察脏器变化情况,并进行H-E染色,光学显微镜下观察脏器的变化;采用免疫组织化学方法检测糖皮质激素受体在下丘脑-垂体-肾上腺轴表达的情况。结果给予激素类药物组动物出现肾上腺明显偏小;组织病理学表现为肾上腺体积显著减少,各层细胞数量减少,排列紧密,即为肾上腺萎缩;垂体,下丘脑未见明显异常变化;与阴性对照组相比,激素药物组大鼠下丘脑、垂体和肾上腺中糖皮质激素受体的表达增加(P<0.05)。结论本试验研究提示糖皮质激素类药物能够增加正常SD大鼠下丘脑-垂体-肾上腺中糖皮质激素受体的表达并伴有肾上腺萎缩现象。并在本实验室建立了下丘脑-垂体-肾上腺轴的病理组织学检查方法和免疫组织化学方法。
OBJECTIVE To examine the change of hypothalamus-pituitary-adrenal axis of normal SD rats after administration of hormone drugs with histopathological and immunohistochemical method under GLP condition,and to set up pathological examination method on hypothalamus-pituitary-adrenal axis and glucocorticoid receptor detection method in the center. METHODS A total of 32 SD rats,16 male and 16 female,were divided into the control group and hormone drug group. Rats of the hormonal drug group were injected with dexamethasone sodium phosphate injection and rats of the control group with 5% glucose solution. After 7 d,the hypothalamus,pituitary,adrenal gland were extracted from animals and detected with anatomical examination and histopathological examination and detected the expression of glucocorticoid receptor in hypothalamus-pituitary-adrenal axis by immunohistochemical method.RESULTS In hormone drug group,rats adrenal were obviously smaller than that of the control group; the size of adrenal gland significantly reduced,the number of cells layers decreased,packed closely and induced adrenal atrophy. Compared with control group,the expression of glucocorticoid receptor was increased in hypothalamus,pituitary and adrenal increased in hormone drug group( P<0.05). CONCLUSION This study shows that the glucocorticoid hormone drugs can increase the expression of glucocorticoid receptor in normal SD rat hypothalamus-pituitary-adrenal and can induce adrenal atrophy. And the hypothalamic-pituitary-adrenal axis histological examination method has been established in the center.

关键词(KeyWords)： 激素类药物;SD大鼠;下丘脑-垂体-肾上腺轴
hormone drugs;SD rats;hypothalamus-pituitary-adrenal axis

Abstract:

Keywords:

基金项目(Foundation): 广州市科技计划项目(201300000053);; 广州市海珠区科技计划项目(2012-CG-01);; 广东省省级科技计划项目(2013B060300002)

作者(Author): 余增才,陈洁君,麦颖琦,吴丽玉,郭秋平
YU Zengcai,CHEN Jiejun,MAI Yingqi,WU Liyu,GUO Qiuping

参考文献(References)：

• [1]陈新谦,金有豫.新编药物学[M].第14版.北京:人民卫生出版社,1997:442.
• [2]何新明,罗颖洁,杨通,等.免疫组织化学染色技术常见问题的研究与探讨[J].中国免疫学杂志,2011,27:1188-1194.
• [3]何书梅,陈宏智.一种快捷安全的动物病理组织石蜡切片制作技术[J].中国兽医杂志,2012,48(1):15-18.
• [4]陈华絮,杨素娇.兔卵巢组织石蜡切片技术的改良[J].生物学杂志,2007,24(5):59-60.
• [5]闫亮珍,乔传令,张建珍,等.致倦库蚊主要组织结构的石蜡切片观察[J].昆虫学报,2011,54(3):373-380.
• [6]陈贵东,沈艳,杨通,等.HE染色细胞核灰染的处理方法比较研究[J].中国组织化学与细胞化学杂志,2014,23(3):261-263.
• [7]王文勇,黄晓峰,王映梅,等.免疫组化技术标准化的探讨[J].细胞与分子免疫学杂志,2011,27(8):927-929.
• [8]张卫琴.免疫组化技术在病理诊断中的应用[J].安徽医药,2012,16(11):1700-1702.
• [9]吴丹桔.免疫组化技术在肿瘤病理诊断中的应用[J].现代诊断与治疗,2013,24(15):3428-3429.
• [10]杜春晓.硬膜外腔药物注射对SD大鼠肾上腺皮质功能、股骨头及腰椎神经的影响[D].南方医科大学,2012.
• [11]钟连生,马道名,陈志强.糖皮质激素受体研究进展[J].国外医学皮肤性病学分册,2005,31(4):199-201.
• [12]王德杰,刘兴国,张东.糖皮质激素受体研究进展[J].现代生物医学进展,2010,10(4):1592-1594.