关键词: 帕金森病, 电-机械活动, 神经型一氧化氮合酶, 血管活性肠肽, 酪氨酸羟化酶

Abstract: Objective To investigate the relationship of the colon dysfunction to electromechanical activity, the expression of neuronal nitric oxide synthase(nNOS) and gastrointestinal regulation peptides in colon of patients with Parkinson's disease. Methods The colon smooth muscle contractility and basic electrical rhythm following 6-hydroxydopamine(6-OHDA) induced neurodegeneration were studied in rats. In the mean time, the Parkinson disease model rats and normal rats were treated with levodopa. Immunohistochemistry was used to stain myenteric and submucosal neurons for nNOS and vasoactive intestinal polypeptide(VIP) and tyrosine hydroxylase(TH) in colon tissues. In addition, Western blotting was used to analyze the expression of TH in colon tissues. Results 1 In untreated PD group, the dominant frequency of slow wave and the percentage of normal slow wave in colon significantly decreased(P<0.05). In addition, the average amplitude of colon contraction also obviously decreased(P<0.05). 2 In levodopa group, the dominant frequency of slow wave in colon increased. And the dominant frequency of contraction significantly increased(P<0.05). 3 The levodopa treated PD group also showed significant increase in the dominant frequency of contraction in colon(P<0.05). However, the average amplitude of contraction and the percentage of normal slow wave in colon significantly decreased(P<0.05). 4 An increase in the intensity of immunoreactivity for nNOS(P<0.05) as well as an increase in the number of nNOS-positive cells were found in the myenteric plexus in untreated PD group and levodopa treated PD group(P<0.05). 5 No significant difference was found among the groups in numbers of VIP neurons in submucosal plexus. 6 Compared with the control group, the TH-positive neurons in the myenteric plexus in untreated PD group significantly decreased(P<0.05). Conclusion PD had directly negative effects on myoelectrical activity in colon. It may influence the colon motility by the decrease of the frequency of slow wave and the smooth muscle contractility. These changes may play an important role in development of constipation. Levodopa had an excitatory effect on colon motility. An excessive production of nitric oxide may cause the inhibition of motility in colon. VIP neurons may not be involved in modulating the colon motility in PD. The decrease of dopaminergic neurons may be responsible for the dysfunction of colon in PD.

Key words: Parkinson's disease, electro-mechanical activity, neuronal nitric oxide synthase, vasoactive intestinal polypeptide, tyrosine hydroxylase