外源性褪黑素对缺氧缺血性脑损伤新生大鼠皮质酮、糖皮质激素受体mRNA的影响及自身受体的变化  

Effect of Exogenous Melatonin on Plasma Corticosterone,Lucocorticoid Receptor mRNA and Change of Autoreceptors in Neonatal Rats with Hypoxic-Ischemic Brain Damage

作　　者：王莹[1] 扬祖铭 朱海娟[2] 何军[3] 孙斌[1] 丁欣[1] 冯星[1] 

机构地区：[1]苏州大学附属儿童医院新生儿科,江苏苏州215003 [2]苏州市立医院儿科,江苏苏州215000 [3]苏州大学第一附属医院血研所,江苏苏州215000

出　　处：《实用儿科临床杂志》2009年第2期132-134,156,共4页Journal of Applied Clinical Pediatrics

摘　　要：目的观察外源性褪黑素对缺氧缺血性脑损伤(HIBD)新生大鼠干预后不同时间点肾上腺组织中褪黑素受体1及糖皮质激素受体mRNA和血浆皮质酮水平的变化。方法7日龄SD大鼠随机分为治疗组、模型组、假手术组和正常组。常压低体积分数氧建立HIBD模型。治疗组新生大鼠腹腔注射褪黑素10mg/kg;模型组和假手术组新生大鼠注射乙醇载体溶液(0.05g/L)10mg/kg;正常组不作任何干预。各组分别于HIBD完成2、4、8、12、24、48h6个时间点摘取其肾上腺组织,采用反转录多聚酶链式反应法半定量测定各组褪黑素受体1及糖皮质激素受体mRNA的表达;暴露心脏,右心室采血,采用放射免疫分析法检测各组血浆皮质酮水平。结果模型组2h肾上腺组织中褪黑素受体1及糖皮质激素受体mRNA表达下调,血浆皮质酮水平显著升高,4h达高峰(Pa<0.05);治疗组血浆皮质酮及肾上腺组织中褪黑素受体1变化均不明显(Pa>0.05),糖皮质激素受体在24h恢复正常生理水平。结论缺氧缺血应激反应刺激下丘脑-垂体-肾上腺皮质系统过度兴奋,引发机体的应激损伤,血浆皮质酮和肾上腺组织的糖皮质激素受体参与HIBD的病理生理过程,外源性褪黑素可能通过自身受体调控应激激素,降低内源性皮质酮水平,使糖皮质激素受体表达上调,减轻HIBD后的过度应激损伤。Objective To observe the changes of plasma corticosterone（CS） and melatonin receptor 1 （ MR1 ） mRNA and glucocorticoid receptor（GR） in adrenal glands of neonatal rats with hypoxic - isehemie brain damage（HIBD） treated with exogenous melatonin. Methods Postnatal 7 - day - old Sprague - Dawley rats were randomly divided into 4 groups： melatonin treated group, model group, sham operated group,normal control group. Rats in melatonin treated group were given exogenous melatonin 10 mg/kg by intra - peritoneal injection, while model and sham operated group with alcohol carrier （0.05 g/L）10 mg/kg,normal control group without intervention. Adrenal glands were obtained at different time points （ 2,4,8,12,24,48 h） after HIBD, semi - quantitative reverse transeriptase polymerase chain reaction （ RT - PCR） analysis was used to measure the expression of MR1 and GR mRNA and Radioimmunoassay（RIA） for plasma corticosterone levels. Resuits The levels of MR1 and GR mRNA decreased at 2 h after HIBD,while plasma eorticosterone raised significantly at the same time and peaked at HIBD 4 h in model group（Po 〈 0.05 ） , paralleling with the stress level. No obvious change of plasma eortieosterone or MRI was found after exogenous melatonin intervention in melatonin treated group（P 〉 0.05） ,and GR mRNA rebounded to the normal at HIBD 24 h. Conclusions GR in the glands may take part in the patho - physiological process of HIBD for the stress reaction. The exogenous melatonin may lower the endogenous cortieosterone through the regulatory function of autorecepors,then up - regulate the GR mRNA,in order to lighten the excessive stress damage of HIBD.

关 键 词：缺氧缺血性脑损伤 褪黑素 褪黑素受体1 糖皮质激素受体 皮质酮 

分 类 号：R722.1[医药卫生—儿科]