不同剂量氢化可的松对早期脓毒性休克大鼠下丘脑-垂体-肾上腺轴的影响

目的观察不同剂量氢化可的松(HC)对早期脓毒性休克大鼠下丘脑-垂体-肾上腺轴(HPA)的影响。方法分2次注射灭活大肠杆菌O111:B4,建立早期脓毒性休克大鼠模型。1.观察不同剂量HC对早期脓毒性休克的作用。模型鼠随机分为休克组、大剂量组(HD组:HC 150 mg/kg)、中剂量组(MD组:HC 20 mg/kg)、小剂量组(LD组:6 mg/kg),并设对照组。监测皮质醇、促肾上腺皮质激素(ACTH)水平,肾上腺、垂体、脑组织病理及糖皮质激素受体(GR)表达。2.观察HPA轴分泌节律性。模型及对照组大鼠各24只。以昼夜24 h为周期,每2h测定各组2只大鼠的皮质醇、ACTH。实验结果采用双因素方差分析。结果对照组ACTH及皮质醇分泌均有24h周期节律性变化。休克实验模型节律性消失。休克组皮质醇水平明显高于对照组(P<0.05)。应用不同剂量HC后,3组皮质醇水平均显著升高,其升高程度与给药量不成比例。3组ACTH水平均较休克组显著升高(Pa<0.05),组间差异无统计学意义。脓毒性休克早期脑组织病理改变较对照组明显(P<0.05),但肾上腺、垂体未见明显病理结构改变。应用HC后,MD、LD组病理损伤评分均降低,以LD组降低最明显,差异显著(P<0.05)。HD组脑组织病理改变与休克组间无明显差异。休克组GR表达显著低于对照组(P<0.05)。MD、LD组GR表达均较休克组有所升高,但仅LD组差异显著(P<0.05),HD组与休克组无明显差异。结论脓毒性休克早期,不需针对HPA轴的时间节律性使用HC;肾上腺及垂体超微结构无明显改变,支持肾上腺功能不全为功能性肾上腺功能不全。中小剂量对垂体、脑组织有一定保护作用。作为糖皮质激素发挥作用的主要结合物GR表达下调。应用HC干预,小剂量使GR表达上调最显著,可更有效的发挥皮质醇作用。

Influence of Hydrocortisone on Secretion of Hypothalamic-Pituitary-Adrenal Axis in Rats with Early Septic Shock

Objective To assess the effects of different doses of hydrocortisone(HC) on rats with early septic shock and observe the change of hypothalamic-pituitary-adrenal(HPA) axis and affecting factors.Methods The early septic shock model was established by interval injection of E.coli O111:B4 in pathogen-free Wistar male rats.1.Different doses of HC in early septic shock were observed.Forty Wistar rats were randomly divided into 5 groups: septic shock group(NS 0.8 mL),high dose group(HD group,HC 150 mg/kg),middle dose group(MD group,HC 20 mg/kg),low dose group(LD group,HC 6 mg/kg),control group.2.The rhythm of HPA axis was obsereved.Experimental animals were divided into septic shock group and control group,each group had 24 rats.The period of day and night was 24 hours,the experimental data were obtained from 2 rats from each group every 2 hours.Results adrenocorticotropic hormone(ACTH) and cortisol secretion of control group had rhythmicity with period of 24 hours,but rhythmicity in septic shock group disappeared.Cortisol level of septic shock group was significantly higher than that of control group(P<0.05).After HC administration,cortisol levels in all 3 groups increased significantly,but the increase of cortisol was not proportional to the dose.ACTH levels in 3 groups were all lower than that of septic shock group(P<0.05),but that of any 2 of the 3 groups had no significance.Compared with control group,the brain tissue had significant difference(P<0.05).No patho-change had found in adrenal and pituitary through photoelectric scope.After administrating different dose HC,pathologic scores of MD and LD both decreased,and that of LD had significance difference(P<0.05).Conclusions In the early septic shock,the ACTH and cortisol secretion rhythmicity is disrupted.That adrenal and pituitary ultrastructure remains similar with those of controls,disclosing that adrenal dysfunction is functional adrenal dysfunction.Medium and small dose of HC can protect pituitary and brain tissue.GR,the major conjugate through glucocorticoid acts,is down-regulated in early septic shock.The effect of small dose on the up-regulation of GR is most significant,and thus can provide the action of cortisol more effectively.