多巴胺受体在大鼠嗅球的表达及其在帕金森病大鼠嗅觉障碍中的作用  

Expression of dopamine receptors in rat olfactory bulb and its role in hyposmia of Parkinson’s disease rat model

作　　者：周立[1] 张大伟[2] 王志勇[1] ZHOU Li;ZHANG Da-wei;WANG Zhi-yong(Department of Anatomy,Xinxiang Medical University , He'nan Xinxiang 453003,China;Department of Pathophysiology,Xinxiang Medical University , He'nan Xinxiang 453003,China)

机构地区：[1]新乡医学院人体解剖学教研室,河南新乡453003 [2]新乡医学院病理生理学教研室,河南新乡453003

出　　处：《解剖学报》2019年第4期411-417,共7页Acta Anatomica Sinica

基　　金：国家自然科学基金(31200897);河南省医用组织再生重点实验室开放课题(KFKT16003)

摘　　要：目的观察多巴胺受体在大鼠嗅球(OB)的表达与分布,探讨左旋多巴(L-DOPA)治疗对帕金森病(PD)大鼠嗅觉的影响。方法采用免疫印迹、免疫荧光等方法观察多巴胺受体在大鼠OB中的表达;6-羟多巴胺(6-OHDA)双侧注射建立PD大鼠模型,检测L-DOPA治疗对PD大鼠嗅觉功能及谷氨酸脱羧酶(GAD)和脑源性神经营养因子(BNDF)表达的影响。结果嗅球内D1和D2两种多巴胺受体亚型表达含量高。D1和D2在颗粒细胞层(GCL)内GAD阳性的γ-氨基丁酸(GABA)能神经元上大量表达,被酪氨酸羟化酶(TH)阳性神经纤维终末包绕。PD大鼠OB内GCL层TH蛋白表达明显下降(0. 05±0. 01 vs 0. 01±0. 00,P<0. 001)。L-DOPA治疗后,PD大鼠找寻食物小球时间显著降低[(624. 4±113. 4) s vs(312. 4±79. 35) s,P<0. 05],OB内BDNF表达显著升高(0. 02±0. 01 vs0. 07±0. 01,P<0. 01)。结论 D1和D2在GCL层GABA能神经元大量表达。L-DOPA治疗可缓解PD大鼠嗅觉障碍,可能与激活OB内GABA能神经元上的D1和D2复合体,进而改善BDNF表达有关。Objective To observe the localization and expression of dopamine receptors in olfactory bulb(OB) of rats and explore the effect of L-levodopa(L-DOPA) treatment on hyposmia in Parkinson's disease(PD) rat model.Methods Western blotting,immunohistochemistry and immunofluorescence were used to observe the expression and localization of dopamine receptors in the OB. PD rat model was established by bilateral 6-hydroxy dropamine(6-OHDA)injection to detect the effect of L-DOPA treatment on the hyposmia and the expression of glutamic decarboxylase(GAD)and brain derived neurotrophic factor(BNDF) of PD rats. Results D1 and D2 receptors were the major subtypes in the OB.D1 and D2 receptors were expressed by GAD positive γ-aminobutyric acid(GABA) ergic neurons in the granule cell layer(GCL) which surrounded by tyrosine hydroxylase(TH) positive nerve fibers. The expression of TH in the GCL layer of PD rats decreased significantly(0. 05±0. 01 vs 0. 01± 0. 00,P< 0. 001). After L-DOPA treatment,the time of finding food balls in PD rats was significantly reduced [(624. 4±113. 4) s vs(312. 4± 79. 35) s,P< 0. 05]and the expression of BDNF in the OB was increased(0. 02 ± 0. 01 vs 0. 07 ± 0. 01,P< 0. 01). Conclusion D1 and D2 are expressed in the GABAergic neurons in the GCL layer of OB. L-DOPA treatment alleviates the hyposmia of PD rats,which may be related to the D1-D2 receptor heteromeractivation and its downstream BDNF expression of GABAergic neurons.

关 键 词：多巴胺受体 嗅球 脑源性神经营养因子 6-羟多巴胺 帕金森病 免疫印迹法 大鼠 

分 类 号：R743.1[医药卫生—神经病学与精神病学]