Effect Of Collgrongjing Decotion On Glial Cell Line-derived Neurotrophic Factor In Parkinson’s Disease Mice

Objectives:Parkinson’s disease(PD) is a neurodegenerative disease. The pathophysiology of PD is the selective and progressive loss of dopaminergic neurons, which can not be relieved by drug treatment. Congrongjing decotion(CRJD), a compound prescription for kidney tonifying formed according to traditional Chinese medicine and clinical experience, has therapeutic effect on PD in clinical. The aim of this study was to investigate the protective effect of CRJD on 1-methyl-4-phenyl-1,2,3,6-terta-hydropyridine(MPTP) induced PD model in mice and observe the expression of glial cell line-derived neurotrophic factor (GDNF) in substantia nigra. This study may explore the possible mechanism of the effectiveness of CRJD.Methods:In this study, C57BL/6 male mice were divided randomly into the following groups:(1) control, (2) MPTP (30mg/kg, i.p.,7days), (3) MPTP+ low dose of CRJD(4g/kg, i.g.,14days, CRJD-L), (4) MPTP+ middle dose of CRJD(8g/kg, i.g.,14days, CRJD-M), (4) MPTP+ high dose of CRJD(16g/kg, i.g.,14days, CRJD-H). To evaluate the therapeutic effect of CRJD, we observe behavioral impairment of MPTP-treated mice. The dopamine neuron protection of CRJD was assessed through the expression of dopamine(DA) and tyrosine hydroxylase(TH). The level of DA in substantia nigra was analyzed through high performance liquid chromatography (HPLC) and the positive cells of TH was be assessed by immunohistochemistry, the expression of TH protein with western blot (WB). We also analyzed the protein expression of GDNF and its receptors, Bcl-2 and Bax to clarify the mechanism.Results:We found that the swimming immobility time in mice model group were increased, the number of rearing of PD model mice were reduce. The PD model mice were appeared behavioral disorder. Compared with model group mice, CRJD group mice enhanced the ability of swimming and independent activity. The results of HPLC showed the reduction of DA level was be inhibited. Through immunohistochemistry, we found that GRJD protected against MPTP-induced the loss of TH positive nerurons. Moreover, CRJD inhibited the expression of GDNF and its receptors decrease. The reduction of Bcl2 was attenuated and the upregulation of Bax was ameliorated in mice treated with CRJD.Conclusion:1.CRJD can increase the content of DA in substantia nigra and improve the expression of TH in MPTP induced PD model mice. CRJD can improve the behavioral disorder.2 CRJD can improve the expression of GDNF and its receptor in MPTP induced PD model mice in substantia nigra..3 CRJD improved the behavior impaired by MPTP and showed the dopamine neuron protection against MPTP toxicity might through enchaned GDNF expression.