6-羟基多巴胺诱导的帕金森病大鼠纹状体 5-羟吲哚乙酸、褪黑素与多巴胺的关系

Relationship of 5-hydroxy indole acetic acid, melatonin and dopamine in rat model of Parkinson＇ s disease induced by 6-hydroxydopamine

目的观察6-羟基多巴胺（6-OHDA）诱导的帕金森病（PD）大鼠纹状体透析液中，5-羟吲哚乙酸（5-HIAA）和褪黑素的动态变化及其与多巴胺的关系。方法脑内单侧双点注射6-OHDA至大鼠右侧黑质致密部和前脑内侧束建立PD模型。用脑微透析术分别于建模后1周、2周、3周、4周的10：00收集毁损侧纹状体透析液，高效液相色谱检测多巴胺、5-ttlAA和褪黑素浓度。结果建模1周PD大鼠的多巴胺浓度为[（1．19±0．22）ng／m1]，明显低于溶剂对照组[（8．62±0．73）ng／m1]和假手术组[（8．73±0．78）ng／m1]（P〈0．01）；PD组的5-HIAA水平呈低于溶剂对照组和假手术组的趋势；PD组褪黑素水平在建模后4周为[（43．31±11．37）pg／m1]，明显高于溶剂对照组[（19．13±5．38）pg／m1]和假手术组（19．80±6．96）pg／m1（p〈0．05）；PD组透析液中多巴胺和5-HIAA浓度具有显著的正相关性（r=0．867，P〈0．01）。结论6-OHDA诱导的PD大鼠纹状体多巴胺减少的同时伴有5-HIAA和褪黑素的变化，这些变化可能与PD的进展相关。

Objective To investigate dynamic changes in extracellular striatal 5-hydroxy indole acetic acid （5-HIAA） and melatonin （MLT） concentrations in the 6-hydroxydopamine （6-OHDA）-induced Parkinson＇ s disease （PD） rat models. Methods A hemiparkinsoninm rat model was established by a unilateral injection of 6- OHDA into the right substantia nigra pars compacta （SNc） and the right medial forebrain bundle （MFB）. Dialy- sate samples were collected at 10：00 in the lesioned striatum by microdialysis at 1,2,3 and 4 weeks post-lesion, respectively. The levels of dopamine （DA） and 5-HIAA,as well as MLT in dialysate samples were measured by high performance liquid chromotorgraphy （HPLC）. Results One week after surgery, the level of DA in PD group was （ 1.19 ± 0.22 ） ng/ml, which was distinctly lower than those in the vehicle group （ （ 8.62 ± 0.73 ） ng/ml） and the sham group （（8.73 ± O. 78） ng/ml） （P 〈 0.01 ）. The levels of 5-HIAA in PD group had a downward trend, but there were no significant differences. The level of MLT in PD group was （43.31 ± 11.37 ）pg/ml at 4 weeks post-lesion,and significantly higher than those in the vehicle group （（ 19.13 ±5.38 ）pg/ml） and the sham group （ （ 19.80 ±6.96）pg/ml） （P〈0.05）. The striatal dialysate DA and 5-HIAA concentrations had a good pos- itive correlation in the PD group （ r = 0. 867, P 〈 0.01 ）. Conclusion Decreased DA level concomitantly with changes of 5-HIAA and MLT in the ipsilateral striatum of 6-OHDA-induced PD rats, and these changes may be re- lated to PD progression.