孕酮通过PI3K/Akt信号通路减轻新生大鼠缺血缺氧性脑损伤  

Progesterone reduce hypoxic-ischemic brain injury in neonatal rats through PI3K/Akt signaling pathway

作　　者：李晓娟[1] 李新娟[1] 朱晓谦[2] 程远[1] 张利彬[1] 王小引[3] 

机构地区：[1]新乡医学院生理学与神经生物学教研室,河南新乡453003 [2]新乡医学院第三附属医院眼科,河南新乡453003 [3]新乡医学院生物化学教研室,河南新乡453003

出　　处：《中风与神经疾病杂志》2014年第6期488-491,共4页Journal of Apoplexy and Nervous Diseases

基　　金：河南省教育厅自然科学研究项目(2008A180029);河南省高等学校青年骨干教师资助计划(2012GGJS-134);新乡医学院重点研究领域招标课题(ZD2011-37)

摘　　要：目的探讨孕酮是否通过PI3K/Akt信号通路减轻新生大鼠缺血缺氧性脑损伤。方法取40只7 d龄新生Wistar大鼠随机分成4组:假手术组:仅做颈部切口,不做缺氧缺血处理;模型组:按动物模型的方法进行缺氧缺血处理;孕酮组:动物进行缺氧缺血处理且在缺氧前30 min按8 mg/kg腹腔注射孕酮溶液;抑制剂组:在建立缺血缺氧性脑损伤模型前30 min,按16μg/kg剂量在大鼠左侧海马区注射Wortmannin。电镜观察新生鼠缺氧缺血性脑损伤神经元的变化,采用免疫组织化学法检测海马pAkt及NF-κB的蛋白表达,应用Western blot检测海马pAkt及NF-κB的蛋白含量。结果 24 h后假手术组神经元结构基本正常,模型组神经元由于缺氧缺血损伤呈空化改变,给予孕酮后的缺氧缺血神经元受损情况改善,空化现象减少,应用抑制剂神经元空化改变明显。缺氧缺血后海马神经元pAkt蛋白表达减少,NF-κB表达增加;孕酮预处理可增加pAkt的表达,降低NF-κB表达;使用抑制剂组pAkt蛋白表达减少,NF-κB表达增加。结论孕酮可通过激活PI3K/Akt信号通路,增加pAkt的水平,抑制NF-κB表达,减轻缺血缺氧性脑损伤中的炎症反应,发挥脑保护作用。Objective To investigate progesterone reducing hypoxic-ischemic brain injury in neonatal rats through PI3K/Akt signaling pathway. Methods 7 days old newborn Wistar rats were randomly divided into four groups, sham group：only with neck incision, without hypoxic-isehemic treatment;model group：with neck incision and hypoxie-ischemic treatment;progsterone group：with hypoxic-ischemic treatment and 8 mg/kg progesterone was injected intraperitoneally 30 min before hypoxia,inhibitor group：30 min before the establishment of HIBD model, 16 μg/kg wortmannin was injected in the left hippocampus. Neuronal changes of hypoxic-isehemic brain were observed under electron microscopy. Protein expressions of pAkt and NF-κB in hippocampus were detected by immunohistochemistry and western blot. Results The neuronal structures in the sham group after hypoxic-ischemie for 24 hours were normal. The neuronal structures in the model group had cavitation changes and the damage reduced after being given progesterone. Inhibitor application increased hypoxic-ischemic neuronal damage. Protein expressions of pAkt decreased and NF-κB increased after hypoxic-ischemic. Progesterone pre- treatment could increase pAkt and reduce NF-κB expression. The inhibitor could reduce pAkt and increase NF-KB expression. Conclusion Through activation of PI3K/Akt signaling pathway, progesterone increase pAkt and decrease NF-κB, reduce the inflammation injury of hypoxic-ischemic brain and play a neuroproteotive role in the brain.

关 键 词：孕酮 缺氧缺血性脑损伤 磷脂酰肌醇3-激酶蛋白激酶B 磷酸化蛋白激酶B 核因子KAPPAB 

分 类 号：R743.3[医药卫生—神经病学与精神病学]