泼尼松与促皮质素致未成熟脑损伤机理的初步探讨.docVIP

泼尼松与促皮质素致未成熟脑损伤机理的初步探讨 王晓宇 曹洁 蔡方成 （重庆医科大学附属儿童医院神经内科，重庆400016） 摘 要：目的 对泼尼松与促皮质素导致脑损伤的机理进行初步探讨。方法选用与人类婴儿期年龄相当的健康婴幼鼠和成年鼠各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，血清血清神经元特异性烯醇化酶（Neuro-specific Enolase，NSE）水平显著升高50.6%～103.2%，长程小剂量给药后其增高达38.3%～60.3%，无显著性差异，且这些NSE升高的组同时伴有Bax蛋白表达显著增强（P0.01）、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。 关键词：泼尼松；促皮质素；未成熟脑；大鼠 中图分类号： R725;R322.81 文献标识码：A  A PRELIMINARY STUDY ON THE PATHOGENESIS OF BRAIN DAMAGE IN INFANT RATS INDUCED BY CORTICOSTEROIDS WANG Xiao-yu,CAO Jie,CAI Fang-cheng（Department of Neurology, Children’s Hospital, Chongqing University of Medical Sciences,Chongqing 400016,China） ABSTRACT：Objective To explore the pathogenesis of brain damage in rats induced by prednisone or corticotrophin initially. Methods 192 Healthy infant and 192 adult 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 further subdivided into 12 subgroups(n=8 in each),including the subgroups of therapeutic-dose with long or short course;the subgroups of therapeutic-dose in withdrawal for 4 weeks after long or short course;the subgroups of low-dose with long or short course,and their corresponding control subgroups. Serum NSE concentration was quantitated by ELISA.Expression of apoptosis-related proteins Bax and Bcl-2 in the brain was detected by immunohistochemistry.Neuronal apoptosis was detected by TUNEL. Result In infant rats treated with prednisone or corticotrophin in therapeutic-dose for short term or long term, serum NSE concentration increased significantly by 50.6%～103.2%.And serum NSE increased by 38.3%～60.3% in infant low-dose long-term groups(though no statistic