长程服用苯巴比妥和托吡酯对幼鼠脑组织中Bcl-2和Bax蛋白的影响

目的探讨长程服用苯巴比妥(PB)和托吡酯(TPM)对幼鼠脑组织中Bcl-2和Bax蛋白的影响。方法将60只日龄18 d的健康SD幼鼠随机分为正常对照组、PB组、TPM组,各20只。根据给药时程又将每个给药组分为2周短程及4周长程给药组,共6组,各10只。PB组给予PB 30 mg·kg-1·d-1灌胃,TPM组给予TPM 40 mg·kg-1·d-1灌胃,正常对照组给予等体积0.9%氯化钠溶液灌胃。3组分别于2周、4周时测幼鼠体质量后采血并处死,称取脑质量,脑组织石蜡包埋,切片,进行苏木素-伊红染色及尼氏染色,光镜下观察脑组织形态变化。用免疫组化方法检测各组大鼠脑切片海马及额叶皮质凋亡相关蛋白Bcl-2和Bax的表达水平。结果短程PB给药组和短程TPM给药组体质量、脑质量及脑组织结构变化与正常对照组比较,差异均无统计学意义(P0.05)。长程PB给药组幼鼠脑质量较正常对照组明显减轻(P0.01),额叶皮质神经元减少,且神经元结构明显异常。长程TPM给药组体质量、脑质量及脑组织结构变化与正常对照组比较,差异均无统计学意义(P0.05)。长程PB给药组幼鼠脑组织额叶皮质Bax蛋白表达水平高于正常对照组(P0.01),Bax/Bcl-2比值高于正常对照组(P0.05)。长程TPM给药组幼鼠脑组织Bax蛋白水平及Bax/Bcl-2比值与正常对照组比较,差异均无统计学意义(P0.05)。结论长程服用PB可引起发育中脑组织明显的组织学损伤及神经元坏死与过度凋亡,幼鼠脑组织额叶皮质Bax蛋白表达显著增强和Bax/Bcl-2比值增高可能是未成熟鼠脑质量减轻和引起脑功能障碍重要原因。长程服用TPM后幼鼠脑组织结构无明显变化。

Influence of Long - term Treatment of Phenobarbital and Topiramate on Bcl - 2 and Bax Protein in Brain Tissue ofYoung Rats

Objective To investigate the influence of long - term treatment of phenobarbital （PB） and topiramate （TPM） on Bcl -2 and Bax protein in brain tissue of young rats. Methods A total of 60 healthy 18 -day -old SD young rats were randomly divided into normal control group, PB group, TPM group, 20 in each. Each group was further derided into long -term （4 weeks） treated group and short- term （2 weeks） treated group randomly, 10 in each. The rats in PB group were given intragastric administration with PB 30 mg ~ kg-l ~ d-~ , the rats in TPM group were given intragastrie administration with TPM 40 mg ~ kg-I . d-1, and the rats in normal control group were given intragastric administration with equal volume of 0. 9% sodium chloride solution. The body and brain weight were measured when the rats were sacrificed after 2 weeks and 4 weeks, brain tissue was embedded in paraffin, hematoxylin - eosin staining and Nissl staining used, changes in brain tissue obversed by light microscope morphological, expression of apoptosis - related proteins Bcl - 2 and Bax in neurons detected by immunohisto- chemistry. Results There were no significant differences in body weights, brain weights and histological changes among short PB administration group, short TPM administration group and normal control group （P 〉 O. 05 ）. The brain weights in long - term treated group of PB was significantly reduced compared with the normal control group （P 〈 0. 01 ）, prefrontal cortical neu- rons decreased and neuronal structures had obvious abnormalities. The body weights, brain weights and structural changes in the long - term treated group of TPM were without statistically significant difference compared with normal control group （P 〉 0. 05）. The rats brain frontal cortex Bax protein and Bax/Bcl - 2 ratio in long - term treated groups of PB was higher than those of normal