CAJ | 학술논문

目的探讨大鼠重型颅脑创伤(traumatic brain injury,TBI)后急性期下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴损害和功能改变的意义.方法成年健康封闭群雄性SD大鼠60只,随机(随机数字法)分为假手术组、模型组和治疗组,每组20只.采用Feeney法建立大鼠重型TBI模型.治疗组于伤后10 min、24 h和48 h腹腔注射地塞米松0.6mg/kg,假手术组和模型组给予等容量生理盐水替代.各组大鼠腹腔注射1μg促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)作刺激试验,分别于伤后第3、12、24、72小时4个时间点进行观察.应用化学发光法测定血清皮质酮(corticosterone,CORT)和ACTH含量.第72小时取大鼠下丘脑、垂体和肾上腺,采用免疫组织化学方法观察白细胞介素6(interleukin-6,IL-6)和肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)表达情况.所得数据采用SPSS 17.0统计软件包进行单因素方差分析和SNK-q检验.结果 ①模型组大鼠伤后第3小时外周血CORT和ACTH达高峰,明显高于假手术组,随后逐渐降低；各时间点ACTH刺激试验后CORT上升的幅度(△max)均低于假手术组(P＜0.05或P＜0.01).治疗组大鼠伤后所有时间点CORT均高于模型组,ACTH仅伤后第24小时高于模型组；ACTH刺激后CORT的△max值均较模型明显升高(P＜0.05或P＜0.01).②模型组大鼠伤后第72小时下丘脑与垂体IL-6、TNF-α阳性细胞数较假手术组明显升高(P＜0.01)；治疗组则较模型组明显降低(P＜0.01)；肾上腺皮质仅IL-6阳性细胞数差异显著(P＜0.01).结论重型TBI大鼠早期即可存在肾上腺皮质功能改变,随着时间推移,对ACTH反应程度降低.小剂量短疗程地塞米松可减轻HPA轴炎症反应程度,增强肾上腺皮质对ACTH的敏感性.
목적 탐토대서중형로뇌창상(traumatic brain injury,TBI)후급성기하구뇌-수체-신상선(hypothalamic-pituitary-adrenal,HPA)축손해화공능개변적의의.방법 성년건강봉폐군웅성SD대서60지,수궤(수궤수자법)분위가수술조、모형조화치료조,매조20지.채용Feeney법건립대서중형TBI모형.치료조우상후10 min、24 h화48 h복강주사지새미송0.6mg/kg,가수술조화모형조급여등용량생리염수체대.각조대서복강주사1μg촉신상선피질격소(adrenocorticotropic hormone,ACTH)작자격시험,분별우상후제3、12、24、72소시4개시간점진행관찰.응용화학발광법측정혈청피질동(corticosterone,CORT)화ACTH함량.제72소시취대서하구뇌、수체화신상선,채용면역조직화학방법관찰백세포개소6(interleukin-6,IL-6)화종류배사인자α(tumor necrosis factor-alpha,TNF-α)표체정황.소득수거채용SPSS 17.0통계연건포진행단인소방차분석화SNK-q검험.결과 ①모형조대서상후제3소시외주혈CORT화ACTH체고봉,명현고우가수술조,수후축점강저；각시간점ACTH자격시험후CORT상승적폭도(△max)균저우가수술조(P＜0.05혹P＜0.01).치료조대서상후소유시간점CORT균고우모형조,ACTH부상후제24소시고우모형조；ACTH자격후CORT적△max치균교모형명현승고(P＜0.05혹P＜0.01).②모형조대서상후제72소시하구뇌여수체IL-6、TNF-α양성세포수교가수술조명현승고(P＜0.01)；치료조칙교모형조명현강저(P＜0.01)；신상선피질부IL-6양성세포수차이현저(P＜0.01).결론 중형TBI대서조기즉가존재신상선피질공능개변,수착시간추이,대ACTH반응정도강저.소제량단료정지새미송가감경HPA축염증반응정도,증강신상선피질대ACTH적민감성.
Objective To study the clinical significance of the injury and functional change of hypothalamic-pituitary-adrenal (HPA) axis after acute severe traumatic brain injury (TBI) in the rats.Methods A total of 60 adult healthy male Spraque-Dawley rats were randomly (random number) divided into 3 groups (n =20 in each group):sham operation group,model group and treatment group.The TBI models of rats were established by Feeney' s method.A low dose of dexamethasone (0.6 mg/kg) was injected into the abdominal cavity 20 minutes,24 hours and 48 hours after injury in treatment group,while rats of sham operation group and model group received equal volume of normal saline instead.All the rats were injected 1 μg adrenocorticotropic hormone (ACTH) into the abdominal cavity.The related parameters were detected at four time points,3 hours,12 hours,24 hours and 72 hours after cerebral contusion.The plasma corticosterone (CORT) and ACTH levels were measured by chemiluminescence.The hypothalamic,pituitary and adrenal of the rats were taken out for observing interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression detecting by immunohistochemical techniques at 72nd hour after TBI.One-way ANOVA and SNK-q test were used to analyze the results with SPSS 17.0 software package.Results The levels of ACTH and CORT on 3rd hour of model group raised remarkably compared with that of sham operation group,then they reduced gradually.The levels of CORT were lower than that of sham operation group at every time points after ACTH stimulation test (P ＜0.05 or P ＜0.01).The levels of CORT at all time points of treatment group were changed remarkably compared with that of model group.However,the ACTH levels of treatment group on 24 h increased slightly than that of model group.And the tendency of them was similar to model group (P ＜ 0.05 or P ＜ 0.01).The number of the hypothalamus and pituitary cells which express IL-6 and TNF-α in model group was more significantly increased when compared with that in sham operation group (P ＜ 0.01),while the number of this kind of cell in treatment group was significantly decreased than that in model group (P ＜ 0.01).The number of the adrenal cortex cells which express IL-6 in treatment group was more significantly decreased when compared with that in model group (P＜ 0.01),while the number of this kind of cell in model group was significantly increased than that in sham operation group (P ＜ 0.01).However,there was no significant difference of the TNF-α between all the groups (P ＞ 0.05).Conclusions Functional change of adrenal occurs early in the severe acute traumatic brain injury rats,and the response of adrenal to ACTH decreased as time goes by.Low-dose,short-course dexamethasone can delay the pathological changes,reduce the inflammatory response of HPA axis and increase the sensitivity of adrenal response to ACTH.