周卫　　胡晓华　　刘克洪　　王晓阳　　白弘照　　袁毅　　高刘传

[摘要] 目的 研究外源性硫化氫对颅脑创伤后应激障碍模型大鼠的神经保护作用及其对核因子Kappa B/抑制蛋白（NF-κB/IκB）调节机制。 方法 60只雄性SD大鼠简单随机化法分为对照组、模型组、低/中/高剂量硫化氢组，每组各12只。对照组常规管理，模型组构建PTSD动物模型。低剂量硫化氢组以幽闭电击法建立PTSD模型，电击前20 min给予1.68 mg/kg硫氢化钠（NaHS）腹腔注射处理;中剂量硫化氢组以幽闭电击法建立PTSD模型，电击前20 min给予3.20 mg/kg NaHS腹腔注射处理;高剂量硫化氢组以幽闭电击法建立PTSD模型，电击前20 min给予6.40 mg/kg NaHS腹腔注射处理。比较各组Morris水迷宫（MWM）评分、大鼠神经损伤严重缺损评分标准（NSS）评分、海马区细胞凋亡灰度值、NF-κB/IκB通路p65、pIκBα/IκBα表达情况，并观察各组海马区细胞形态学特征。 结果 模型组逃避潜伏期、NSS评分高于对照组，穿越平台位置次数、在原平台所在象限的时间占比低于对照组（P<0.05）;硫化氢组以上指标改善显著（P<0.05）;高剂量硫化氢组与对照组逃避潜伏期、穿越平台位置次数、在原平台所在象限的时间占比、NSS评分比较，差异无统计学意义（P>0.05）; 模型组海马区细胞凋亡灰度值高于其他各组（P<0.05）;硫化氢组灰度值改善显著（P<0.05）。模型组p65、pIκBα/IκBα高于对照组（P<0.05），硫化氢组改善明显（P<0.05）。 结论 外源性硫化氢对颅脑创伤后应激障碍模型大鼠具有神经保护作用，可减少海马区细胞的凋亡，抑制NF-κB/IκB通路表达，并呈现出剂量依赖性，NF-κB/IκB丰富生理功能为PTSD多靶点治疗提供了新思路。

[关键词] 颅脑创伤;神经保护;NF-κB/IκB;外源性硫化氢;应激障碍

[中图分类号] R563.8          [文献标识码] A          [文章编号] 1673-9701（2021）11-0030-06

The neuroprotective effect of exogenous hydrogen sulfide on rats with post-traumatic stress disorder and the mechanism of its regulation on NF-κB/IκB

ZHOU Wei HU Xiaohua LIU Kehong WANG Xiaoyang   BAI Hongzhao   YUAN Yi   GAO Liuchuan

Department of Rehabilitation， Zhejiang Provincial Armed Police Corps Hospital， Hangzhou   310051， China

[Abstract] Objective To study the neuroprotective effect of exogenous hydrogen sulfide on rats with post-traumatic stress disorder and the mechanism of its regulation on nuclear factor Kappa B/inhibitory protein （NF-κB/IκB）. Methods Sixty male SD rats were randomly divided into the control group， the model group， and the low/medium/high-dose hydrogen sulfide group，with 12 rats in each group. The control group was routinely managed， and the model group buildt PTSD animal models. The low-dose hydrogen sulfide group was treated with a claustrophobic electric shock to establish a PTSD model， and 1.68 mg/kg sodium hydrosulfide（NaHS） was injected intraperitoneally 20 minutes before the electric shock. The medium-dose hydrogen sulfide group was treated with a claustrophobic electric shock to establish a PTSD model， which was given 3.20 mg/kg NaHS intraperitoneal injection treatment 20 minutes before the electric shock. The high-dose hydrogen sulfide group was treated with claustrophobic shock method to establish PTSD model， and 6.40 mg/kg NaHS intraperitoneal injection treatment was given 20 minutes before the shock. The Morris water maze（MWM） scores， the scores of severe neurological deficits（NSS） scores， hippocampal cell apoptosis gray values，NF-κB/IκB pathway p65， pIκBα/IκBα expression in each group were compared. The hippocampus cell morphology characteristics in each group were compared. Results The escape latency and NSS scores of the model group were higher than those of the control group. The number of crossing the platform and the proportion of time in the quadrant of the original platform of the model group were lower than those of the control group（P<0.05）. The above indicators in the hydrogen sulfide group improved significantly（P<0.05）. There was no statistically significant difference between the hydrogen sulfide group and the control group in the escape latency， the number of crossing the platform position， the proportion of time in the quadrant where the original platform was located， and the NSS score（P>0.05）. The gray value of apoptosis in the hippocampus of the model group was higher than that of the other groups（P<0.05）. The gray value of the hydrogen sulfide group improved significantly（P<0.05）. The p65 and pIκBα/IκBα in the model group were higher than those in the control group（P<0.05）， and the hydrogen sulfide group improved significantly（P<0.05）. Conclusion Exogenous hydrogen sulfide has a neuroprotective effect on post-traumatic stress disorder model rats. It can reduce hippocampal cell apoptosis and inhibit the expression of NF-κB/IκB pathway in a dose-dependent manner.The abundant physiological functions of NF-κB /IκB provide new ideas for multi-target therapy of PTSD.

[Key words] Craniocerebral trauma; Neuroprotection; NF-κB/IκB; Exogenous hydrogen sulfide; Stress disorder

创伤后应激障碍（Post-traumatic stress disorder，PTSD）是由于个体遭受创伤或应激事件而导致的精神障碍，病程较长，可达数月或数年[1]。PTSD的临床治疗方法包括药物治疗与心理干预，其发生发展的生物学机制为临床研究的热点。国外科学家Goodwin在1989年首次检测到脑内游离硫化氢，能通过减少谷氨酸合成释放、抗氧化等调控神经系统，参与情绪、学习能力等调节。PTSD的主要临床表现为情绪异常以及学习能力的下降，因此有学者提出，可以尝试通过补充外源性硫化氢来提升PTSD的治疗效果。……