[1]王晓宇,曹洁,蔡方成.泼尼松与促皮质素致未成熟脑损伤机制的初步探讨[J].第三军医大学学报,2008,30(24):2316-2320.
 WANG Xiao-yu,CAO Jie,CAI Fang-cheng.Pathogenesis of brain damage in infant rats induced by corticosteroids[J].J Third Mil Med Univ,2008,30(24):2316-2320.
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泼尼松与促皮质素致未成熟脑损伤机制的初步探讨(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
30卷
期数:
2008年第24期
页码:
2316-2320
栏目:
论著
出版日期:
2008-12-30

文章信息/Info

Title:
Pathogenesis of brain damage in infant rats induced by corticosteroids
作者:
王晓宇 曹洁 蔡方成
重庆医科大学附属儿童医院神经内科
Author(s):
WANG Xiao-yu CAO Jie CAI Fang-cheng
Department of Neurology, Children’s Hospital, Chongqing Medical University, Chongqing 400016, China
关键词:
泼尼松促皮质素未成熟脑大鼠
Keywords:
prednisone corticotrophin immature brain rats
分类号:
R-332;R743.802;R977.11
文献标志码:
A
摘要:
目的    对泼尼松与促皮质素导致脑损伤的机制进行初步探讨。    方法    婴幼大鼠(7日龄)和成年大鼠(2月龄)各192只,分为泼尼松婴幼组、泼尼松成年组、促皮质素婴幼组和促皮质素成年组共4个大组(n=96),每大组再分为长、短程治疗剂量组以及相应用药后停药4周组,长、短程小剂量组以及相应用药后停药4周组,及对照组等共计12个观察组(n=8)。对各组血清中NSE水平、脑内Bax与Bcl-2蛋白表达以及神经细胞进行检测。    结果    短、长程治疗剂量给予婴幼鼠泼尼松或促皮质素后,血清神经元特异性烯醇化酶(Neuro-specific Enolase,NSE)水平较对照组显著升高,其幅度达50.6%~103.2%;长程小剂量给药后其增高幅度为38.3%~60.3%(P>0.05),但这些NSE升高的组同时伴有Bax蛋白表达显著增强(P<0.01)、Bax/Bcl-2比值增高(1.91~2.40倍之间)和TUNEL阳性细胞表达的增多。而成年鼠仅在治疗剂量泼尼松或促皮质素长程给药后见血清NSE及免疫组化、TUNEL等各项指标有显著异常。停药4周后,婴幼鼠或成年鼠各组的各项指标与对照组相比均不再有显著差异。    结论    过度凋亡与坏死过程的激活是导致婴幼期激素脑损伤的重要机制。
Abstract:
Objective    To explore the possible pathogenesis of brain damage in rats induced by prednisone or corticotrophin.     Methods    The doses of prednisone or corticotrophin were determined by a primary experiment to obtain corresponding plasma cortisol or corticosterone level as same as that in sick children after drug taking. Then 192 healthy infant (at the age of 7 d) and 192 adult (at the age of 2 months) male SD rats were divided into 4 groups as infant prednisone group, adult prednisone group, infant corticotrophin group and adult corticotrophin group (n=96 in each). then every group was further subdivided into 12 subgroups (n=8 in each). The subgroups were divided according to the dose (therapeutic or low doses), the course [short (10 d) or long (3 weeks)], the sacrificed time (24 h or 4 weeks after withdrawal), and their corresponding controls. Serum neuron-specific enolase (NSE) concentration was quantified by ELISA. Expressions of apoptosis-related proteins, Bax and Bcl-2 in the brain were detected by immunohistochemical assays. Neuronal apoptosis was detected by TUNEL.     Results    Our primary experiment indicated that the therapeutic dose was 4 mg·kg-1·d-1 or 150 U·m-2·d-1 for prednisone or corticotrophin, and the small dose was 2 mg·kg-1·d-1 or 38 U·m-2·d-1 for them. In infant rats treated with prednisone or corticotrophin at therapeutic-dose for short or long term, their serum NSE concentration were increased significantly by 50.6% to 103.2%. And serum NSE was increased by 38.3% to 60.3% in infant after low-dose treatment for long term. Over-expression of Bax protein (P<0.01), increase of Bax/Bcl-2 ratio (1.91 to 2.40 times) and more TUNEL-positive neurocyte were detected in these above groups. In adult groups only those treated with therapeutic-dose prednisone or corticotrophin for long term displayed above mentioned features.     Conclusion    Excessive apoptosis and initiation of process death are the important mechanism of brain damage induced by prednisone or corticotrophin.

参考文献/References:

王晓宇, 曹洁, 蔡方成. 泼尼松与促皮质素致未成熟脑损伤机制的初步探讨[J].  第三军医大学学报, 2008, 30(24):2316-2320.

更新日期/Last Update: 2008-11-12