帕金森病（PD）已不再是黑质变性所致的区域性神经疾病，而是累及中枢和外周的全身性疾病，在出现运动症状前，98.6%的患者会出现一些非运动症状，以胃肠道功能障碍发生率最高。然而，PD胃肠道功能障碍的中枢机制尚不清楚。在前期工作中，我们观察到PD早期Ghrelin含量降低，可能是导致胃肠道功能障碍的原因之一，为了探讨其机制，拟在携带人突变型alpha-突触核蛋白的PD转基因小鼠和慢性鱼藤酮灌胃小鼠PD模型上，观察疾病不同时期胃肠道功能变化与Ghrelin含量、ENS和DMV神经元功能之间的关系，及其与黑质多巴胺能神经元功能改变之间的关系，进一步在Ghrelin受体敲除的PD转基因小鼠上验证，并评价Ghrelin的早期干预效果。本研究将证实PD早期胃肠道功能障碍的出现是由于ENS和DMV神经元功能障碍，导致Ghrelin含量降低所致，早期应用Ghrelin干预能够改善症状并延缓疾病进程。

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons originating in the substantia nigra. Braak hypothesized that alpha-synuclein spreads through the brain in a predictable ascending manner and proposed a 6-step pathological staging system for PD. This early pathological change in the enteric nervous system (ENS) and dorsal motor nucleus (DMV) is pertinent to consideration of the pathophysiology of delayed gastric emptying in early PD. Gastrointestinal dysfunction is common in all stages of PD, accounting for 98.6% PD patients. However, the central mechanisms underlying the gastrointestinal dysfunction in PD remain largely unknown. Our previous studies show decreased plasma ghrelin levels in the early stage of PD patients, which might partially accounts for the gastrointestinal dysfunction. To further illustrate the underlying mechanism, in the present study, we detected the changes of the gastrointestinal motility in different stages of PD. Meanwhile, the plasma ghrelin levels and function of ENS and DMV neurons are also determined. The changes of motor activity and degeneration of nigral dopaminergic neurons are also observed. The changes of the gastrointestinal motility and motor activity are detected, as well as the neuronal function of ENS, DMV and subtantia nigra. Two kinds of PD animal models are used in this study, one is PD transgenic mice expressing the prion promoter driven human A53T mutation, the other is chronic PD models by employing an intragastrical rotenone intoxication. Since ghrelin is a hormone with potential as a therapeutic agent for delayed gastric emptying and also as a novel neuroprotective agent in PD, intravenous injection of ghrelin is applied to the two PD models in the very early stage. The results are further strengthened in PD transgenic mice with ghrelin receptor GHSR knockdown. This study could supply some evidence that dysfunctions of ENS and DMV neurons in early PD stages result in impaired release of ghrelin, which might account of the disturbed gastrointestinal motility. Early application of ghrelin might improve the symptoms and delay the progression of PD.