丙酸睾酮预处理对新生鼠缺氧缺血性脑损伤的保护作用及其机制研究  

Study on protective effect and its mechanism of pretreatment of testosterone propionate on hypoxic-ischemic brain damage in the neonatal rats

作　　者：李占魁[1] 赵春燕[2] 冯晋兴[3] 沈凌[1] 柯华[1] 

机构地区：[1]西安交通大学医学院第二附属医院儿科,陕西西安710004 [2]川北医学院附属医院儿科 [3]深圳市儿童医院新生儿科

出　　处：《中华妇幼临床医学杂志（电子版）》2006年第5期250-253,共4页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：国家自然科学基金项目资助(编号:30471827)

摘　　要：目的观察丙酸睾酮(testosteronepropionate,T)预处理对缺氧缺血性脑损伤(HIBD)新生鼠皮质及海马区雄激素受体(androgenreceptor,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。方法新生3d龄SD大鼠随机分为3组,1正常对照组(n=24);2HIBD组(n=24),3T预处理组(n=24)。T预处理组大鼠于3d龄时给予T预处理。HIBD组和T预处理组大鼠于7d龄时进行HIBD模型制作。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,间接检测神经细胞坏死和凋亡。并于HI后24h,72h,7d制作石蜡切片,用免疫组化法观察各组大鼠大脑皮质和海马AR表达的动态变化。结果HIBD组大脑皮质和海马区细胞数明显比正常对照组减少,差异有显著意义(P<0.05),而T预处理组神经元坏死较HIBD组有所减轻,差异有显著意义(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,细胞凋亡少见。HI后24h,72h和7d,正常对照组和HIBD组大鼠脑皮质和海马区仅见极少量AR阳性细胞表达,而T预处理组大鼠于HI后24h和72hAR表达水平明显增多(P<0.05)。结论T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,减轻神经细胞凋亡,从而发挥神经保护作用。Objective To observe the effects of testosterone propionate （T） pretreatment on AR expression and neural necrosisand apoptosis so as to explore the possible mechanism. Methods 3-day-old Sprague-Dawley （SD） rats were randomly divided into three groups：①control group （n= 24）, ② HIBD group （n=24） ,③ pretreatment with T group （n=24）. Pretreatment with T group was pretreated at 3 day old. Making HIBD model on 7-day-old SD rats of HIBD and pretreatment with T 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 12 h,24 h,72 h,7 d 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 T group showed lesssevere damages than HIBD group, seldom seeingapoptosis. 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 T 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 24 h,72 h,7 d after HI, while the expression of AR positive cells in pretreatment with T group increased apparently at 24 h and 72 h after HI（P〈0.05）. Conclusion T 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 allev

关 键 词：脑缺氧 脑缺血 丙酸睾酮 雄激素受体 神经生长因子 

分 类 号：R722.1[医药卫生—儿科]