前庭核H1受体在运动病发生中的作用

目的研究H1受体在大鼠脑干前庭核的表达及其在运动病发生和信号转导过程中的作用。方法24只健康SD大鼠（200g～250g，雌雄各半）依随机数字表法随机分为4组，每组6只。A：对照组，不接受运动刺激和抗运动病药物；B：仅暴露运动刺激组；C：仅接受抗运动病药物组（H，受体阻断剂盐酸异丙嗪，0．25mg／只，腹腔注射）；D：接受运动刺激和抗运动病药物组。通过旋转摆动复合运动刺激诱使大鼠发生运动病，以出现对糖精水的厌饮症状作为运动病发病指标。测定运动刺激后及暴露其他相应实验因素后45min内各组小鼠0．15％糖精水的饮用量。通过免疫荧光染色观察大鼠脑干前庭核H。受体的分布；蛋白印迹法分析大鼠前庭核层面脑干组织H1受体蛋白的表达，并观察运动刺激和异丙嗪对H1受体表达的影响。结果各组大鼠平均糖精水饮用量有明显差异（F=346．82，P〈0．01）。运动刺激组平均糖精水饮用量明显少于对照组，差异有统计学意义（P〈0．01）。异丙嗪组平均糖精水饮用量与对照组相近（P〉O．05）。应用异丙嗪后接受运动刺激组的平均糖精水饮用量多于运动刺激组（P〈O．01），但仍明显少于对照组及异丙嗪组（P〈0．01）。免疫荧光染色显示，大鼠脑干前庭核表达有H1受体，运动刺激可使其表达增加，但未受到异丙嗪的明显抑制。蛋白印迹法分析显示，大鼠前庭核层面脑干组织有H1受体蛋白的表达，运动刺激亦使其表达增加，异丙嗪对其表达增加不具有明显的抑制作用。结论旋转摆动复合运动刺激可有效地诱发大鼠发生运动病。大鼠脑干前庭核存在有H1受体，运动刺激可使其表达增加。异丙嗪具有一定的抗运动病作用，但对运动刺激所诱发的大鼠脑干前庭核H1受体表达增加没有明显的抑制作用。其作用机制可能是与组胺竞争性地结合H1受体而非通过影响H1受体的表达。

Implication of histamine H1 receptors in vestibular nucleus and motion sickness

Objective To investigate the expression of histamine H1 receptors (H1 R) in vestibular nucleus of rat' s brainstem and the underlying role of H1R in motion sickness (MS).Methods Total of 24 healthy Sprague-Dawley rats were randomly divided into four groups,6 rats in each group.A:MS(-)/Drug(-) control group,in which the rats were not exposed to motion stimulus and no anti-motion sickness drug promethazine taking； B:MS(+)/Drug(-) group,only exposed to motion stimulus; C:MS(-)/Drug(+) group,that applied with promethazine but not exposed to motion stimulus； D:MS(+)/Drug (+) group,applied with promethazine (0.25 mg for each rat) 30 minutes before exposing to motion stimulus.MS was induced by a complex motion stimulus and the conditioned taste aversion was used as the behavioral indicator of MS in rats,measuring the intaked volume of 0.15％ sodium saccharin solution (SSS) for each rat 45 minutes after motion stimulus.H1 R in the vestibular nucleus of brainstem was examined by immunofluorescence staining.The expression of H1 R proteins in hrainstem tissue at vestibular nucleus level was detected by Western blot.The effects of motion stimulus and anti-MS drug promethazine on the expressions of H1R were evaluated.Results The mean intake of SSS in B group was significantly less than that in A group (F=346.82,P＜0.01),which demondtrated that MS was induced by this motion stimulus in the rats.The mean intaked SSS volume (14.8 ml) in C group was similar to that in A group (P＞0.05),indicating no significant effect of promethazine on intaking SSS.The mean intaked SSS volume in D group was more than that in B group (P＜0.01),but less than that in A group or C group (P＜0.01),which indicated that the inhibited intaking of SSS in motion-stimulated rats was improved partially by promethazine.Immunofluorescence staining showed the positive expression of H1R in the vestibular nucleus of brainstem in rats and the expression was enhanced by motion stimulus,but was not significantly affected by promethazine.Western blot analysis showed that H1 R proteins expressed in the brainstem tissues at vestibular nucleus level,which were also increased significantly after motion stimulus,but the increase was not affected by promethazine.Conclusions H1 R exists in vestibular nucleus of brainstem in rats.The expression of H1R is up-regulated by motion stimulus,but is not affected by anti-MS drug promethazine.It indicates that histaminergic system is involved in the development of MS.Promethazine,as a blocker H1R,plays the role of anti-MS by binding H1R rather than by increasing the expression of H1R.