Abstract: Objective To analyze the relationship between serum IL-17A level, hippocampal IL-1β, TNF-α mRNA expression and post-stroke depression (PSD) in rats, to explore the pathophysiological mechanism of PSD. Methods 30 adult specific pathogen free (SPF) SD male rats were randomly divided into sham operation group, stroke group and PSD group. Baseline behavioral assessment was conducted for each group. The rats in stroke group and PSD group were treated with ischemia reperfusion after middle cerebral artery occlusion (MCAO), then 1 week later, the rats in PSD group were treated with chronic unpredictable mild stress (CUMS) stimulation, 1 or 2 kinds of stimulation per day and for 4 weeks. After 4 weeks stimulation, behavior assessments were made in all the groups again. Whereafter, the expression of serum IL-17A in all the rats was detected by ELISA, the morphology of neurons in the hippocampus of each group rats was observed by Nissl staining, and the mRNA expressions of IL-1β and TNF-α in the hippocampus were also detected by real-time quantitative PCR. The express level of inflammatory factors in serum and hippocampus area and hippocampus lesions in PSD were analyzed. Results The level of serum IL-17A in the sham operation group, stroke group and PSD group was 18.56±2.56 pg/mL, 40.78±4.13 pg/mL and 52.10±5.22 pg/mL, respectively, and the difference among the three groups was statistically significant. The relative expression level of IL-1β mRNA in the hippocampus of rats in the sham operation group, stroke group and PSD group was 0.570±0.322, 2.617±0.128 and 3.189±0.107, respectively, and the difference among the three groups was statistically significant. The relative expression level of TNF-α mRNA in the hippocampus of rats in the sham operation group, stroke group and PSD group were 0.999±0.007, 1.258±0.042 and 1.623±0.041, respectively, and the difference among the three groups was statistically significant. Nissl staining indicated that neurons in hippocampus CA1 region were damaged in stroke group and PSD group, with the most serious damage in PSD group. Conclusions The serum IL-17A level of rats in PSD group was up-regulated, and the mRNA of IL-1β and TNF-α in the hippocampus were highly expressed, which indicated that inflammatory reaction may be involved in the pathophysiological mechanism of PSD.

Key words: Post-stroke depression; Interleukin-17A; Interleukin -1β; TNF-α; Hippocampus

摘要：

目的 分析卒中后抑郁（post-stroke depression，PSD）大鼠血清IL-17A水平、海马I L-1β、TNF-α mRNA 表达的变化，探讨PSD的病理生理机制。 方法 将30只成年的无特定病原体级SD雄性大鼠随机分为假手术组、卒中组、PSD组，对各组大鼠 进行基线行为学评估，其中卒中组和PSD组大鼠行大脑中动脉闭塞（middle cerebral artery occlusion， MCAO）缺血再灌注处理，1周后对PSD组大鼠行慢性轻度刺激（chronic unpredictable mild stress，CUMS）， 每天给予1～2种刺激，连续4周，CUMS刺激4周后对各组大鼠进行行为学评估。评估结束后采用尼氏 染色观察各组大鼠海马区神经元形态，使用ELISA方法检测大鼠血清中IL-17A水平，实时荧光定量PCR 检测大鼠海马IL-1β、TNF-α mRNA表达。观察PSD情况下，血清及海马神经元炎症因子的表达水平及 海马损伤情况。 结果 假手术组、卒中组和PSD组大鼠血清的IL-17A水平分别为18.56±2.56 pg/mL、40.78±4.13 pg/mL和 52.10±5.22 pg/mL，三组比较差异有统计学意义；假手术组、卒中组、PSD组大鼠海马区IL-1β mRNA相 对表达水平分别为0.570±0.322、2.617±0.128和3.189±0.107，三组比较差异有统计学意义；假手术 组、卒中组、PSD组大鼠海马区TNF-α mRNA基因相对表达水平分别为0.999±0.007、1.258±0.042和 1.623±0.041，三组比较差异有统计学意义；尼氏染色提示卒中组、PSD组海马区CA1区神经元存在损 伤，以PSD组最明显。 结论 PSD组大鼠血清IL-17A水平上调，海马I L-1β、TNF-α mRNA高表达，提示PSD发生的病理生理 机制中可能有炎症反应参与。

关键词: 卒中后抑郁; 白细胞介素-17A; 白细胞介素-1β 、肿瘤坏死因子-α 海马