缺血性脑损伤大鼠对应激反应性的实验研究  

Experimental study on the responses to stress after cerebral ischemic injury in rats

作　　者：刘立[1] 郭俊[2] 段小莉[3] 马超[4] 张翠玲[5] 张晓梅[1] 王百忍[3] 

机构地区：[1]第四军医大学航空航天医学系临床医学教研室 [2]第四军医大学唐都医院神经内科,西安710032 [3]第四军医大学全军神经科学研究所 [4]第四军医大学西京医院心血管外科 [5]解放军第五医院干部病房

出　　处：《卒中与神经疾病》2007年第3期134-137,共4页Stroke and Nervous Diseases

摘　　要：目的探讨缺血性脑损伤大鼠对轻度束缚应激的反应性。方法通过阻断大脑中动脉(MCAO)建立缺血性脑损伤大鼠模型,术后第5周开始行2周束缚应激,应激结束后处死大鼠,脑组织HE染色明确缺血灶,免疫组化法检测大鼠脑内Fos和促肾上腺皮质激素释放因子(CRF)蛋白表达水平。结果单纯MCAO组(M)和MCAO+应激组(MR)大鼠可见明确缺血灶,损伤侧大脑半球萎缩和脑室扩大,光镜观察缺血区大量核固缩,坏死灶周边神经胶质细胞增生;MR组大鼠下丘脑室旁核、杏仁核中央亚核及终纹床核Fos和CRF阳性神经元明显多于其他组,差异有统计学意义(P<0.05)。结论缺血性脑损伤后大鼠脑内Fos和CRF蛋白表达对应激的反应性增强,CRF通过前反馈机制持续激活下丘脑-垂体-肾上腺轴并导致抑郁可能是脑卒中后抑郁发生的主要机制之一。Objective To investigate the responses to mild restraint stress after cerebral ischemic injury in rats. Methods Healthy male Sprague-Dawley rats were established as models of cerebral ischemic injury by intraluminal filament occlusion to left middle cerebral artery（MCAO） for 60 minutes. All rats were divided randomly into MCAO＋ stress group（MR, n = 12）, MCAO group （M, n = 12）, Sham＋ stress group （SR, n = 12） and Sham group （S, n = 12）. Repeated restraint stress （2 hours/day） was performed from the fifth week after surgery for 2 weeks. At the end of stress scheme, all rats were killed. The ischemic foci were identified by utilizing hematoxylin and eosin （HE） staining. In addition, Fos and CRF expressions after restraint stress in rats were assessed by immunohistochemistry. Results The ischemic regions appeared azury in HE staining in M and MR groups. There was a distinct boundary between ischemic regions and normal tissues. Cerebral infarct existed throughout the middle cerebral artery territory. Besides, there were obvious tissue atrophy and cerebral ventricular enlargement in ischemic hemisphere. Light microscopic observation showed that nerve cells were distributed in an extremely atactic order in ischemic region. There were a large number of karyopyknosis phenomena and neuroglial cell proliferation around the necrosis loci. Besides, the rats in MR group expressed Fos and CRF-like immunoreactivity strongly in the paraventricular hypothalamic nucleus （PVN）, central sub- nucleus of Amygdala（CeA） and bed nucleus of stria terminalis（BNST） in the brain slices, showing a signifi- cant difference from other groups （P（0. 05）. Conclusions There is an increased sensitivity of Fos and CRF expressions to mild restraint stress in some cerebral nuclei which are related to regulating stress responses and emotion. CRF can lead to the occurrence of depressive disorders by stimulating continuously HPA axis activi- ties in a positive feedback manner, which may be one major pathoge

关 键 词：脑缺血 束缚应激 抑郁 FOS 促肾上腺皮质激素释放因子 

分 类 号：R749.13[医药卫生—神经病学与精神病学]