帕金森病大鼠中缝背核内5-HT、CRF及其受体CRFR2的表达变化  

Expression changes of 5-TH,CRF and CRFR2 in the dorsal raphe nucleus of rats with Parkinson's disease

作　　者：马璐璐[1] 付文玉[2] 庄文欣[3] 刘长山[4] 王晓晓[2] 栾守婧 王倩[1] 

机构地区：[1]潍坊医学院人体解剖与组织胚胎学省级重点实验室,潍坊261041 [2]潍坊医学院组织胚胎学教研室,潍坊261041 [3]潍坊医学院医学研究实验中心,潍坊261053 [4]潍坊市人民医院内分泌科,潍坊261041

出　　处：《神经解剖学杂志》2014年第4期463-468,共6页Chinese Journal of Neuroanatomy

摘　　要：目的:观察5-羟色胺(5-HT)、促肾上腺皮质激素释放因子(CRF)及其受体CRFR2在神经毒素6-羟多巴胺(6-OHDA)诱导的帕金森病(PD)大鼠中缝背核内的表达变化,探讨PD与抑郁的关系。方法:采用脑立体定位术将6-OHDA注射至大鼠一侧中脑黑质致密部和前脑内侧束,制备大鼠PD模型。10只制模成功的PD大鼠为模型组,10只注射生理盐水的正常大鼠为对照组。采用免疫组织化学染色法观察中缝背核内5-HT、CRF、CRFR2阳性细胞的分布、形态和数量变化。采用逆转录聚合酶链式反应法检测5-TH合成的限速酶-色氨酸羟化酶2(TPH2)mRNA,CRF mRNA及CRFR2 mRNA的表达变化。结果:对照组大鼠中缝背核5-HT阳性神经元为中等大小,胞质呈棕色,模型组细胞体积略小,染色较浅。中缝背核的CRF和CRFR2阳性细胞分布区域与5-HT神经元一致。CRF细胞胞体呈圆形或三角形,CRFR2阳性细胞胞体呈椭圆形或梭形。对照组CRF、CRFR2阳性细胞数量较少,染色较浅,模型组数量多,染色深。与对照组相比,模型组5-HT阳性细胞的数量和TPH2 mRNA相对表达量均明显减少(P<0.01),而CRF、CRFR2阳性细胞的数量和CRF mRNA及CRFR2 mRNA相对表达量均显著增加(P<0.01)。结论:大鼠中缝背核内5-HT、CRF及CRFR2的表达变化与6-羟多巴胺诱导的帕金森病密切相关。Objective： To explore the expression changes of depression-related neuroendohormones 5-hydroxytryptamine （5-HT）, corticotropin-releasing factor （CRF） and CRF type 2 receptor （CRFR2） and their mRNAs in the dorsal raphe nucleus （DRN） of 6-OHDA induced Parkinson＇s disease （PD） rats, to discuss the relationship between PD and depression. Methods： Male adult Sprague-Dawley （SD） rats were microinjected with 6-OHDA into the right substantia and medial forebrain bundle of the brain to set up the PD rat models. Ten PD rats served as model group, and 10 adult normal rats were injected saline instead of 6-OHDA as the control group. The distribution, morphology and the number change of expression of 5-HT, CRF and CRF receptor 2 （CRFR2） in DRN of rats in two groups were examined by immunohistochemical methods. The expressions of tryptophan hydroxylase 2 （TPH2 is 5-HT synthesis rate-limiting enzyme） mRNA, CRF mRNA and CRFR2 mRNA were detected by reverse transcription polymerase chain reaction. Results： 5-HT-positive neurons of DRN in control group were medium-sized, with brown cytoplasm, but in the model group the 5-HT-positive neurons were smaller and lighter. The regional distribution of CRF- and CRFR2-positive neurons and 5-HT-positive neu- rons were the same. The CRF-positive neuronal soma in DRN was showed round or triangular and the CRFR2-positive ceils were oval or spindle. Both the CRF- and CRFR2-positive ceils in model group were darker. The number of 5-HT positive cells and expression quantity of TPH2 mRNA in DRN of the PD rats were reduced significantly （ P 〈 0.01 ）, but the numbers of the CRF and CRFR2 positive cells and the expression quantity of CRF mRNA and CRFR2 mRNA were increased remarkably compared with those of the normal rats （P 〈 0.01 ）. Conclusion： The expression changes of 5-HT, CRF and CRFR2 in dorsal raphe nucleus of rat are closely associated with PD induced by 6-OHDA.

关 键 词：帕金森病 中缝背核 抑郁 促肾上腺皮质激素释放因子 5-羟色胺 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]