外源性黄体酮对新生小鼠缺血缺氧性脑损伤的神经保护作用  

The neuroprotective effects of exogenous progesterone on hypoxic- ischemic brain injury in neonatal mice

作　　者：周洁[1] 陆俊杰[2] 祖洁[1] 刘洁 金国良[1,4] 周妍[1,4] 韩晶晶[1,4] 花放[1,4,5] 

机构地区：[1]徐州医学院附属医院神经内科,江苏徐州221002 [2]徐州市中心医院神经内科,江苏徐州221009 [3]徐州市第六人民医院神经内科,江苏徐州221006 [4]徐州医学院神经系统疾病研究所,江苏徐州221002 [5]江苏省麻醉学重点实验室,江苏徐州221004

出　　处：《徐州医学院学报》2016年第4期244-248,共5页Acta Academiae Medicinae Xuzhou

基　　金：国家自然科学基金（81271268,81571469）;2012年江苏特聘教授项目;江苏省2014年双创团队项目

摘　　要：目的研究外源性黄体酮对新生小鼠缺血缺氧性脑损伤（hypoxic／ischemicinjury，HI）的神经保护作用及其分子机制。方法40只出生后7日龄雄性野生型（C57BL／6J）小鼠被随机分为假手术＋生理盐水组（WS）、假手术＋黄体酮组（WSP）、缺血缺氧＋生理盐水组（WT）、缺血缺氧＋黄体酮组（WTP）。小鼠于HI后24h断头取脑，应用ELISA方法检测脑组织内的炎症因子白细胞介素-1α（IL-1α）和IL-6的表达；另-亚组于HJ后72h，经心脏灌注处死，取脑，冰冻切片，应用尼氏染色评价梗死面积和脑组织损伤，应用Fluoro-JadeB（F-JB）染色检测神经元死亡。结果缺血缺氧可以导致新生小鼠脑组织坏死和神经元死亡。与缺血缺氧组相比，外源性黄体酮治疗组的脑梗死面积和神经元死亡明显减少（P〈0．05）。缺血缺氧可促进脑组织内炎症因子IL-1和IL-6的释放，外源性黄体酮治疗可以抑制缺血缺氧诱导的IL-1和IL-6的释放（P〈0．05）。结论黄体酮可减少新生小鼠缺血缺氧脑组织的坏死和神经细胞死亡，其对炎症反应的调节作用可能是其作用机制之一。Objective To investigate the effect of exogenous progesterone on hypoxic - ischemic injury. （HI） in neonatal mice and the mechanisms of action. Methods Forty male C57BL/6J neonatal mice aging seven days were ran- domly assigned into four groups： a sham and normal saline group （WS）, a sham and progesterone group （WSP）, a hy- poxia/ischemia and normal saline group （WT）, and a hypoxia/ischemia and progesterone group （WTP）. Then, the mice were sacrificed 24 h later to determine the levels of IL - 1 α and IL - 6 in the brain by ELISA. Meanwhile, 72 h af- ter HI, mice were sacrificed to collect the brain tissues which were then cut into frozen sections. The area of infarction and cerebral damage were measured using Nissl staining, while neuronal death was detected using Fluoro -Jade B （F- JB） staining. Results HI induced neuronal death and tissue necrosis. Compared with the HI group, neuronal death and infarction area were reduced significantly in the progesterone treatment group （ P 〈 0.05 ）. HI increased the levels of IL - 1 α and IL - 6 in neonatal mice, which could be inhibited after progesterone exposure （P 〈 0.05 ）. Conclusion Exoge- nous progesterone can attenuate neuronal death and brain tissue injury in neonatal mice, which may be associated with in- hibition of inflammatory responses.

关 键 词：黄体酮 缺血缺氧脑损伤 新生小鼠 

分 类 号：R722.12[医药卫生—儿科] R743.3[医药卫生—临床医学]