机构地区:[1]陕西省妇幼保健院新生儿科,西安700003 [2]深圳市儿童医院新生儿科 [3]西安交通大学医学院第二附属医院儿科
出 处:《中国新生儿科杂志》2008年第1期35-38,共4页Chinese Journal of Neonatology
基 金:国家自然科学基金项目(30471827);陕西省自然科学基金项目(004C263)
摘 要:目的探讨雄激素对缺氧缺血性脑损伤(HIBD)的保护作用及其机制。方法制作新生鼠HIBD模型,随机分为假手术组(8只)、HIBD对照组(32只)、雄激素干预组(32只)(与模型制成后即刻注射丙酸睾丸酮25mg/kg),与HI后6、24、48h,7d取脑组织制作石蜡切片,用免疫组化法观察Bcl-2和Bax蛋白在各组大鼠皮质和海马表达的动态变化。结果新生大鼠海马及皮层均有Bcl-2和Bax表达,但Bax表达较微弱;在HI后6hBcl-2表达开始呈阳性反应,HI后24hBcl-2表达明显增多,72h后达高峰,7d后逐渐减低;Bax的表达在HI后24h达高峰,72h后逐渐降低,7d后维持在低水平;雄激素干预后Bcl-2和Bax的表达变化时程与缺氧缺血对照组相似;HI后6、24、72h,Bcl-2在皮层和海马的表达水平明显高于对照组,差异均有统计学意义(P分别<0.05,0.05,0.01),HI后7d两组间差异无统计学意义(P>0.05)。雄激素组Bax的表达水平在HI后24h显著低于对照组(P<0.05);在HI后6、72h,7d两组Bax的表达差异无统计学意义(P>0.05)。结论雄激素可抑制缺氧缺血后神经细胞凋亡而发挥脑保护作用,可能与雄激素上调Bcl-2蛋白,下调Bax蛋白表达有密切关系。Objective To study the protective effect of androgen, and its mechanism on neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods 7 days old Sprague-Dawley (SD) rats were selected for this study. They were made into HIBD models and then randomly divided into 9 groups, including Sham operated group, HIBD group and androgen group. The rats in androgen group were treated with testosterone propionate (25 mg/kg) after HIBD were established. Their brain tissues were harvested at 6, 24, 48 hours and 7 days after establishment of HIBD and their expression of Bcl-2 and Bax protein in cortex and hippocampal CA regions were measured by immunohistochemical methods. Results The expression of Bcl-2 and Bax were positive in cortex and hippocampus of rats in sham operation group, but the expression of Bax was very weak. The expression of Bcl-2 began to become positive at 6 hours after HIBD, it increased significantly at 24 hours and peaked at 72 h ; then it decreased steadily after 7 d. The expression of Bax peaked at 24 hours and decreased steadily after 72 hours, it maintained at low level after 7 d. The changes of expression of Bcl-2 and Bax in androgen group were similar to that in HIBD group. The level of expression of Bcl-2 in cortex and hippocampus of rats in androgen group was higher than its in HIBD group at 6 h, 24 h and 72 h, the differences were statistically significant ( P 〈 0. 05, 0. 05, 0. 01 respectively) ; there was no significant differences between the two groups at 7 days (P 〉 0. 05 ). The level of expression of Bax of in androgen group was significantly lower than its in HIBD group (P 〈 0. 05 ) at 24 h after, there was no significant differences between the two groups at 6 h, 72 h and 7 d (P 〉 0. 05 ). Conclusions It is shown that androgen may play protective role by inhibiting apoptosis of nerve cells of rats after HIBD. Its mechanism may be related to up-regnlation of Bcl-2 protein and down-regulation of Bax protein.
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