多巴胺受体调节对新生大鼠缺氧缺血性脑损伤后焦虑样行为的影响

Impact of dopamine receptor modulation on reduced anxiety-like behavior in neonatal rats after hypoxic-ischemic brain damage

摘要:

目的 观察缺氧缺血性脑损伤（HIBD）新生大鼠远期黑质酪氨酸羟化酶（TH）的表达及焦虑样行为的变化以及多巴胺（DA）受体拮抗剂干预对其远期焦虑样行为的影响。方法 将120 只7 日龄（P7）SD大鼠分为正常对照组、假手术组、HIBD 组及HIBD+DA 受体拮抗剂组。Rice 法制作HIBD 模型；假手术组予右侧颈总动脉分离，但不予结扎和低氧处理；HIBD+DA 受体拮抗剂组在造模前后予腹腔注射DA 受体拮抗剂，其余组予等量的生理盐水腹腔注射。各组分别于P14、P21 及P28（n=10）进行高架十字迷宫（EPM）实验检测动物的焦虑样行为及应用免疫组织化学方法测定其大脑黑质TH 的表达。结果 P21 及P28 时HIBD 组开放臂停留时间（OT）及开放臂次数比率较正常对照组、假手术组及HIBD+DAR 组增高（P<0.05），且HIBD+DAR 组OT较正常对照组增高（P<0.05）。P14、P21 及P28 时HIBD 组及HIBD+DAR 组TH 水平均低于正常对照组及假手术组，且HIBD 组低于HIBD+DAR 组（P<0.05）。结论 初生时给予DA 受体拮抗剂能改善HIDB 对青春期焦虑样行为的异常作用并能减轻多巴胺能神经元的损伤。

Abstract:

Objective To observe the long-term changes in anxiety-like behavior and tyrosine hydroxylase (TH) expression in the substantia nigra (SN) after hypoxic-ischemic brain damage (HIBD) in a neonatal rat model and to further explore the relationship between dopamine (DA) level and long-term anxiety-like behavior using the DA receptor (DAR) antagonist. Methods Seven-day-old (P7) neonatal Sprague-Dawley (SD) rats were randomized into normal control, sham-operated, HIBD and HIBD+DAR antagonist groups. HIBD model was prepared by ligating the right common carotid artery and 8% hypoxia exposure. The rats in the sham-operated group were sham-operated and were not subjected to right common carotid artery ligation and hypoxia exposure. The DAR antagonist was injected intraperitoneally before and after inducing HIBD. The same amount of normal saline was given to the other three groups as a control. Anxiety-like behavior was evaluated by elevated plus maze test, and TH expression in the SN was measured by immunohistochemistry on P14, P21, and P28. Results On P21 and P28, the time spent in the open arms and the percentage of open arms entries in the HIBD group were significantly increased compared with those in the normal control, sham-operated and HIBD+DAR antagonist groups (P<0.05); in addition, the HIBD+DAR antagonist group showed a significantly longer time spent in the open arms than the normal control group (P<0.05). On P14, P21, and P28, TH expression in the HIBD and HIBD+DAR antagonist groups was significantly lower than that in the normal control and sham-operated groups, and TH level in the HIBD group was significantly lower than that in the HIBD+DAR antagonist group (P<0.05). Conclusions DAR antagonist allows the restoration of anxiety-like behavior and alleviates the damage to dopaminergic neurons in SD rats after HIBD.