大剂量糖皮质激素应用过程中早期给予 ACTH 大鼠下丘脑－垂体－肾上腺轴的功能及病理变化

摘要

目的：观察大剂量糖皮质激素（GC）应用过程中早期给予促肾上腺皮质激素（ACTH）大鼠下丘脑－垂体－肾上腺（HPA）轴的功能及病理变化。方法将30只健康雄性 Wistar 大鼠随机分为正常组、对照组和治疗组，每组10只。正常组予蒸馏水灌胃2周，对照组和治疗组用大剂量醋酸泼尼松水溶液灌胃2周；之后治疗组加用ACTH 皮下注射2周，其余两组灌胃方法不变。分别于实验开始时、实验满2周时、实验满4周时测定大鼠血清皮质醇及 ACTH；实验满4周时处死各组大鼠，测大鼠垂体、肾上腺质量并观察其病理形态，计算大鼠脏器指数。结果实验开始时各组大鼠血清皮质醇及 ACTH 水平相近（P 均＞0．05）。实验满2周时，对照组和治疗组大鼠血清皮质醇及 ACTH 水平相近（P 均＞0．05）。实验满4周时，治疗组大鼠血清皮质醇和 ACTH 水平较对照组升高（P 均＜0．05），且垂体和肾上腺的质量及其脏器指数也较对照组升高（P 均＜0．05）。实验满4周时，各组大鼠垂体远侧部未见明显改变；正常组大鼠肾上腺皮质束状带结构清晰，对照组较正常组束状带变薄且结构紊乱；治疗组与对照组相比束状带增厚、细胞核增多，但较正常组结构排列紊乱。结论大剂量 GC 应用过程中早期给予 ACTH 可减轻GC 对大鼠 HPA 轴的抑制作用，促进其皮质醇和 ACTH 的分泌，促进其垂体和肾上腺的增生，并能明显改善其肾上腺皮质的萎缩情况。%Objective To observe the functional and pathological changes of hypothalamic-pituitary-adrenal (HPA) axis of rats in the early-stage application of adrenocorticotropic hormone (ACTH)during the process of using a large dose of glucocorticoid (GC).Methods Thirty male Wistar rats were randomly divided into the normal group,control group and ACTH treatment group,10 rats in each group.Rats of the normal group were given distilled water by gavage for 2 weeks. Rats of the control group and ACTH treatment group were treated with high dose of prednisone acetate in aqueous solution by gavage for 2 weeks.After that,the ACTH treatment group was treated with subcutaneous injection of ACTH for 2 weeks, and the other two groups were treated with the same treatment as before.The levels of cortisol and ACTH in serum were measured respectively at the beginning of the experiment,at the end of 2 and 4 weeks after the experiment.When the ex-periment was over 4 weeks,the rats were killed,the quality of the pituitary and adrenal glands were measured,the patho-logical changes were observed,and organ index was calculated.Results At the beginning of the experiment,there was no difference in the serum cortisol and ACTH between the groups (P >0.05).At the end of 2 weeks after the experiment, there was no significant difference in serum cortisol and ACTH between the control group and the ACTH treatment group (P>0.05).At the end of 4 weeks after the experiment,the serum cortisol and ACTH levels in the ACTH treatment group were higher than those in the control group (all P <0.05),and the quality of pituitary,adrenal gland and organ index were higher than those of the control group (all P <0.05).At the end of 4 weeks after the experiment,no significant changes were found in the distal part of the pituitary of rats in each group.And the structure of adrenal cortex zona of rats in the nor-mal group was clear.The structure of adrenal cortex zona of the control group was thinning and disordered as compared with that of the normal group.The structure of adrenal cortex zona of the ACTH treatment group was thickening and the nucleus increased at different degrees as compared with that of the control group,but it arranged in disorder as compared with that of the normal group.Conclusion Early application of ACTH in the process of using high dose GC can reduce the inhibito-ry effect of GC on HPA axis in rats,accelerate the adrenal cortex zona secretion,promote the proliferation of pituitary and adrenal gland,and improve the adrenal cortex zona atrophy in pathology significantly.