【摘  要】  目的 观察丙酸睾酮（T）预处理对缺氧缺血性脑损伤（HIBD）新生鼠脑皮质及海马区雄激素受体（AR）表达及神经细胞坏死和凋亡的影响,探讨其保护作用的可能机制。方法 3日龄SD大鼠随机分为3正常对照组(n=24)、HIBD组(n=24)、T预处理组(n=24)。T预处理组大鼠于3日龄时给予T预处理。HIBD组和T预处理组7日龄时制作HIBD模型。于缺氧缺血（HI）后12h、24h、72h、7d观察各组脑组织病理形态及应用Nissl染色法测定神经元数目观察神经细胞坏死和凋亡。并于HI后24h、72h、7d制作石蜡切片，免疫组化法观察脑皮质和海马AR表达的动态变化。结果HIBD组脑皮质和海马区细胞数较正常对照组明显减少﹙P﹤0.05﹚，T预处理组神经元坏死较HIBD组有所减轻﹙P﹤0.05﹚，缺血侧(左侧)神经细胞排列较整齐、结构较完整，神经元变性、坏死程度均较HIBD组轻，少见细胞凋亡。HI后24h、72h和7d，正常对照组和HIBD组脑皮质和海马区仅见极少量AR阳性细胞表达，而T预处理组于HI后24h 和72h AR表达水平明显增多﹙P﹤0.05﹚。结论 丙酸睾酮预处理可明显增加HIBD新生大鼠脑皮质和海马区AR的表达水平, 减轻脑皮质及海马区的神经元坏死和凋亡程度，从而发挥神经保护作用。其可能的机制是T通过上调AR表达，介导阻断HI后的瀑布反应,延缓细胞凋亡，减少神经元坏死，从而起到神经保护作用

【关键词】脑缺氧；脑缺血；丙酸睾酮；雄激素受体；

 

Study on protective effect and its mechanism of pretreatment of testosterone propionate on hypoxic-ischemic brain damage in the neonatal rats  LI Zhan-kui, Zhao Chun-yan ,Fang Jin-xing, et al. Department of pediatrics, the Second Hospital of Xi’an jiaotong University

【Abstract】 Objective: To observe the effects of testosterone propionate pretreatment on AR expression and neural necrosisand apoptosis so as to explore the possible mechanism. Methods: 3-day-old Sprague-Dawley (SD)  rats wererandomly divided into three groups: (1) control group (n=24)， (2) HIBD group (n=24) ，(3) pretreatment with testosterone propionate group (n=24). Pretreatment with testosterone propionate group was pretreated at 3 day old. Making HIBD model on 7-day-old SD rats of HIBD and pretreatment with testosterone propionate groups. Observing  changes  of  brain neuropathology and indirectly detecting nerve cell necrosis and apoptosis by Measuring number of nerve cells using Nissl staining  and  to view the dynamic changes of AR expression in cortical and hippocampal neurons of every group rats employing immunohistochemical method in every group on 12h、24h、72h、7d after HI. Results: Nerve cells of ischemic side (left side) hemisphere in HIBD group showed significant damages including indistinct cell structure, derangement of array, nerve cell degeneration,  necrosis,  cell collapse, massive apoptotic cells, reactive hyperplasia of glial cells; nerve cells of

ischemic side (left side) hemisphere in pretreatment with testosterone propionate group showed less severe damages than HIBD group, seldom seeing apoptosis. Adopting Nissl staining, analyzing by image acquiring and analysis system of computer, the density of cortical and hippocampal neurons in HIBD group decreased obviously  compared with control group﹙P﹤0.05﹚, while degree of neuron loss in pretreatment with testosterone propionate group was relieved than HIBD group﹙P﹤0.05﹚. Viewing a small quantity of AR positive cells in cortex and hippocampus of control and HIBD groups at 24h、72h、7d after HI, while the expression of AR positive cells in pretreatment with testosterone propionate group increased apparently at 24h and 72h after HI﹙P﹤0.05﹚. Conclusion: Testosterone propionate pretreatment could apparently up-regulate AR expression on cortex and hippocampus in neonatal rats after HIBD to  reduce. levels of cellular necrosis and apoptosis on cortex and hippocampus alleviated to compare with purely HIBD group after HI. Suggesting that pretreatment of extrinsic androgen could decrease impairment in HIBD.

[作者简介} ,李占魁，男,河南灵宝人,西安交通大学第二医院儿科教研室副主任,副教授,硕士研究生导师. 主攻方向为新生儿缺氧缺血性脑病。主持国家自然科学基金一项、省部级课题两项,获陕西省科技进步二等奖、西安交通大学科学技术一等奖各一项，发表科研论文30余篇。

通讯地址：西安市西五路157号西安交通大学医学院第二附属医院儿科学教研室（710004）；

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