组胺合成酶抑制剂α-FMH对帕金森病大鼠旋转行为和脑内多巴胺及组胺能神经元的影响

EFFECTS OF α-FLUOROMETHYLHISTIDINE,AN IRREVERSIBLE INHIBITOR OF HISTIDINE DECARBOXYLASE,ON TURNING BEHAVIOR AND DOPANERGIC AND HISTAMINERGIC NEURONS IN 6-HYDROXYDOPAMINE-LESIONED RATS

目的探讨内源性组胺在PD发病中的作用。方法采用6-羟基多巴(6-OHDA)制备偏侧毁损的PD大鼠模型,连续7 d侧脑室给予组胺合成酶抑制剂α-FMH(12.5μg,25μg)以降低脑内组胺的含量。术后第7 d观察如下指标:阿朴吗啡诱导的旋转行为;免疫组织化学法检测黑质内多巴胺能神经元和下丘脑后部结节乳头核(TMN)内组胺能神经元的免疫反应活性;高效液相色谱法检测纹状体内多巴胺的含量。结果与模型组相比,α-FMH(25μg)明显降低了阿朴吗啡诱导的PD大鼠的旋转行为(4.09与6.18 r/min相比,P<0.05);延缓了毁损侧黑质内多巴胺神经元的缺失;轻微地增加了纹状体内多巴胺的含量。此外,与假手术组相比,模型组和α-FMH给药组大鼠TMN内组胺能神经元均无明显改变。结论内源性组胺介入了PD的发病机制,但并不伴有组胺能神经元的病理改变。

Objective To investigate the role of endogenous histamine in Parkinson disease. Methods 6-OHDA- lesioned rats were prepared by the conventional mothod, and in the meantime a group of rats were administrated with α- fluoromethylhistidine（α-FMH）, an irreversible inhibitor of histidine decarboxylase （HDC）, via intracerebroventricular injection （12.5μg or 25μg, i.c.v. ） for seven days. On the 7 day, the apomorphine-induced turning behavior and were detected, and the immunoreactivity of dopaminergic neurons in the substantia nigra pars compact （SNc） and histaminergic neurons in the tuberomammillary nucleus （TMN） were evaluated by tyrosine hydroxylase （TH） and HDC immunohistochemistry, respectively, Additionally, the level of dopamine in striatum was determined with high performance liquid chromatography（ HPLC）. Results α- FMH （25μg, i.e.v. ） significantly reduced the turning behavior and prevented the loss of dopaminergic neurons in the SNc, and slightly increased dopamine level in the striatum. Whereas, the immunoreactivity of histaminergic neurons in the TMN of hypothalamus in both the 6-OHDA lesioned and the α-FMH treated rats was not changed. Conclusion Endogeneous histamine may involve in the pathological processes of PD. However, the histaminergic neurons are not involved in PD.