脓毒症早期大鼠下丘脑-垂体-肾上腺轴超微结构变化与功能的关系

The relationship of ultrastructure and function of hypothalamus-pituitary-adrenal axis in early stage of sepsis in rats

目的观察脓毒症早期下丘脑-垂体-肾上腺（HPA）轴结构及功能的变化，并探讨其相互关系。方法雄性SD大鼠30只，按随机数字表法均分为正常对照组、假手术组和脓毒症组。采用盲肠结扎穿孔术（CLP）制作脓毒症大鼠模型，术后6h取血并处死动物，检测血浆促肾上腺皮质激素（ACTH）、皮质酮（CORT）以及下丘脑促肾上腺皮质激素释放激素（CRH）水平；透射电镜下观察HPA轴的超微结构改变。结果脓毒症组血浆ACTH、CORT和下丘脑CRH水平均明显高于正常对照组和假手术组[ACTH（pmol／L）：5．78±0．36比1．94±0．31、2．51±0．10；CORT（nmol／L）：88．48±4．47比22．02±1．62、34．20±2．51；CRH（μg／L）：101．92±6．61比61．65±6．05、66．65±4．03，P〈0．05或P〈0．01]。透射电镜下观察：脓毒症组大鼠下丘脑粗面内质网囊状扩张、脱颗粒，高尔基体肿胀，垂体ACTH细胞分泌颗粒增多，肾上腺组织脂滴减少。结论脓毒症早期大鼠HPA轴处于过度激活状态，血浆ACTH、CORT和下丘脑CRH水平明显升高；HPA轴的超微结构明显改变，且与功能变化有密切联系。

Objective To observe the changes in uhrastructure and function of hypothalamicpituitary-adrenal axis （HPAA）, and to approach the relationship between them in early stage of sepsis in rats. Methods Thirty male Sprague-Dawley （SD） rats were randomly divided into normal control group, sham group, sepsis group. The sepsis model was reproduced by cecal ligation and puncture （CLP）. The rats were sacrificed after collection of blood at 6 hours after CLP, and the levels of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） in the plasma, and the corticotropin release hormone （CRH） in the tissue of hypothalamus were detected. The histopathological changes in HPAA were observed with transmission electron microscopy. Results The levels of ACTH and CORT in plasma, and the CRH in hypothalamus tissue of sepsis group were increased in the early stage of sepsis compared with the normal comrol group or sham group [ACTH （pmol/L）： 5.78 ±0. 36 vs. 1.94 ± 0.31, 2.51 ± 0. 10; CORT （nmol/L） ： 88. 48±4.47 vs. 22.02±1.62, 34.20±2.51; CRH （/xg/L） ： 101.92±6.61 vs. 61.65 ±6.05, 66.65±5 4. 03, P〈 0. 05 or P〈 0. 011. The changes in ultrastructure of the hypothalamus, pituitary and adrenal were also found. In sepsis group, the ultrastructure of hypothalamus was as follows. Rough endoplasmic reticulum expansion and degranulation of rough endoplasmic reticulum, and swelling of Golgi complex were found. A large number of endocrine granules could be seen in ATCH ceils in the pituitary with depletion of adrenal lipid droplets. Conclusion In septic rats, the HPAA was excessively activated, and ACTH and CORT in plasma, and CRH in hypothalamus were significantly increased in early stage of sepsis. The changes in ultrastructure of HPAA were obvious, and the change in function was closely related to the uhrastructural changes.