Effects Of Chinese Medicine Of Central Neurotransmitters,Neurons And Rotational Behaviour In A Rat Model Of Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disorder involving progressive degeneration of dopamine neurons in the substantia nigra. The cause of the disease is remain unknown; however, increasing evidence suggests that free radical-mediated oxidative stress has a major impact on the pathogenesis of PD. Therefore, antioxidation may contribute to the treatment of the disease. Evidence showed that Glutathione(GSH) had anti-oxidation effect, and Ligustrazine and Salvia miltiorrhiza are also suggested to be involved in the reducing oxidative damage evoked by reactive radicals. In 6-hydroxydopamine(6-OHDA)-lesioned rats, an Salvia miltiorrhiza on central neurotransmitters,neurons and rotational behaviour of the disease.ObjectiveTo investigate the effects of GSH, Ligustrazine and Salvia miltiorrhiza on monoamine transmitters, TH neurons, and rotation behaviour, in hemiparkinsonian rats induced by 6-OHDA. To elucidate the possible mechanisms involved in.MethodsMale SD rats were divided into five groups (n=8) at random: control rats, 6-OHDA-lesioned rats without treatment,and 6-OHDA-lesioned rats treated with GSH, Ligustrazine or Salvia miltiorrhiza. 6-OHDA(12 u g/u 1 ) was injected into right substantia nigra pars compacta(SNpc) by two sites of the rat at day 0. In treatment groups, GSH(12mg/Kg/d), Ligustrazine(50mg/Kg/d) or Salvia miltiorrhiza (2.5ml/Kgfd) was i.p. injected everyday from day 0 to day 14 to each rat. After 2 weeks,rotationary behaviour was successfully induced by APO i,p.injection(>5 tums/min) from all rats. Five rats from each group with similar rotationary behaviour were selected for TH immunohistochemistry study and the quantitation of TH neuron. Extracellular dopamine(DA) and its metabolites (DOPAC,HVA) in the striarum of all groups were measures by microdialysis and high preformance liquid chromatography with electrochemical detection (HPLC-ECD) after 2 months.Results1. The controls had no rotational behaviour, all other rats groups showed rotational asymmetry after APO injection.However, there were no significant difference between treated and non-treated groups.2. Immunohistochemistry study showed that the numbers of TH neurons in control group are much higher than other groups. There were no signifinant differences between non-treated and treated groups.3 . In controls, extracellular DA and its metabolites DOPAC, HVA were significantly higher than those of other groups in right sides. Compared with the rats without treatment, the rats treated with Ligustrazine, GSH showed significant higher amount of DA, but not DOPAC and HVA.ConclusionIn 6-OHDA-induced rat model of PD,GSH, Ligustrazine and had no protective effect on neurons, but could increase the level of DA in striatum significantly. The treatments did not change the rotation behaviour. The mechanisms involved in are not so clear.