慢性应激抑制卒中后大鼠海马内源性神经干细胞增殖和分化研究

目的 观察慢性应激对卒中后海马内源性神经干细胞增殖和分化的影响。方法 将雄性SD大鼠分为正常、卒中、慢性应激组。建立左侧大脑中动脉闭塞卒中动物模型并予以慢性不可预见温和应激刺激结合孤养。经溴脱氧尿苷嘧啶（BrdU）标记，免疫组化、荧光双标染色及共聚焦成像动态检测并比较各研究组大鼠左侧海马齿状回BrdU及其与神经元核性蛋白（NeuN）共表达。结果 与卒中组相比，慢性应激组大鼠病灶侧海马齿状回BrdU+细胞数在脑梗死后第7天未见减少，第21天明显减少（28.5±1.9 vs 72.2±1.4），差异有统计学意义（P<0.001）。与卒中组相比，慢性应激组大鼠病灶侧海马齿状回BrdU+/NeuN+细胞比例在脑梗死后30 d（69.0±3.4）%）]和45 d（78.3±2.4）%]均明显减少，差异有统计学意义（P<0.001； P<0.01）。结论 慢性应激能明显抑制卒中后海马内源性神经干细胞的增殖和分化，可能是卒中后抑郁发病的因素之一。

Chronic Stress Inhibits Stroke-induced Proliferation and Differentiation of Endogenous Neural Stem Cells in Rat Hippocampus

Objective To investigate the effect of chronic stress on stroke-induced endogenous neural stem cells (NSCs) in rat hippocampus.Methods Male SD rats were divided into control, stroke and chronic stress treated group. The animals were subjected to consistent focal cerebral infarcts through left middle cerebral artery occlusion (MCAO), followed by 18-day exposure to chronic mild stress (CMS) along with single housing, and then brodmodeoxyuridine (BrdU) labeled. The dynamic expression of BrdU and its co-expression with neuronal nuclear antigen (NeuN) in the left dentate gyrus of hippocampus were determined by immunohistochemistry or double-lable immunofuorescence staining.Results Compared with ischemic animals, in the left dentate gyrus, animals treated with chronic stress had signifcantly less BrdU-positive cells at Days 21 after ischemia (28.5±1.9 vs 72.2±1.4, P<0.001), and decreased proportion of BrdU-positive cells co-stained with NeuN at Days 30 (69.0±3.4)%] and 45 (78.3±2.4)%] (P<0.001 and P<0.01 respectively).Conclusion Chronic stress inhibits stroke-induced proliferation and differentiation of endogenous neural stem cells in hippocampus. It may be one of the etiologies of post-stroke depression (PSD).