Synergistic Treatment Mechanism Of L-dopa-induced Dyskinesia Using Traditional Chinese Medicine And L-dopa

Parkinson's disease (PD) is a nervous system degenerative disease which commonly exists in the elderly. The clinical diagnosis is made by the presence of bradykinesia, postural instability, resting tremor and rigidity. Dopamine (DA) precursor L-dopa is considered clinically as the most effective drug to treat the signs and symptoms of Parkinson's disease, but it causes motor complications that limit its utility. L-dopa-induced dyskinesia (LID; abnormal involuntary movements,AIM) is the most general phenomenon that may affect all parts of the body in an idiosyncratic mixture of chorea (rapid movements that seem to flow from one body part to another), dystonia (slow twisting movements) and myoclonus (jerky muscle contractions), which seriously affect the daily life of PD patients. At present, there are no more efficient therapeutic options for LID except using dopamine receptor agonist to alleviate the symptom. Current research of LID is focus on aspects of extrinsic dopamine volatility stimulation; synergism of dopamine receptor D1 and D2; glutamine receptor affectation on the "direct pathway" and expression change of relative genes and proteins of LID. The Traditional Chinese Medicine (TCM) we used is a compound, which has been used clinically for years as a synergistic treatment of motor complications induced by L-dopa. This TCM has already been proved have a good effect. The synergistic mechanism could be constituted with anticholinergics functions; receptor agonist; antioxidation and regulation of relative gene expression, which is as our mean interest.Two point side lesions' surgery was been taken by injecting 6-OHDA in to rat midbrain substantia nigra to establish PD rat model, which will then through an intraperitoneal injection one month with L-dopa to develop LID. The LID rat models are later treated with saline, L-dopa, TCM, TCM&L-dopa respectively for another one month. Whereafter, the LID rat model are been sacrificed to analysis the oxidative stress, expression of mRNA and dopamine receptor, affinity of dopamine receptor taking the methods of FQ-PCR, Radio-ligand Receptor Binding Assay etc.Among the 80 lesion surgery rats we got 40% successful PD rat model, in which then 25 rats became LID rat model. After two weeks treatment, the TCM and saline group have significant reduce of AIM scores than control group, while parallel significant reduce of AIM scores appears at the fourth week in TCM&L-dopa group compare to L-dopa group. In four weeks treatment, compare to L-dopa group, TCM treated with L-dopa has a remarkable affect on Limb dyskinesia and Masticatory dyskinesia. During 120 minutes scanning, synergistic treatment with TCM shows evident alleviate of AIM at 90th minutes than L-dopa group.According to the FQ-PCR results of lesioned substantia nigra, VMAT2 mRNA expression highly augments in TCM group than in others compare to control. It's also increase more in TCM&L-dopa group than inL-dopa group. This trend also exist in TH and DAT mRNA expression, but less obvious than in VMAT2.D1, D2 mRNA expressions have great increase after treating with TCM in both TCM and TCM&L-dopa groups than in control, especially the D2 mRNA in TCM group. Results of Radio-ligand Receptor Binding Assay indicate that the expression of dopamine receptor D2 in TCM&L-dopa group increased at the same time as the rise of its affinity concern to L-dopa group.All in all, we arrive to the conclusion that this kind of TCM used as synergistic treatment of L-dopa could abate the Limb dyskinesia and Masticatory dyskinesia, and at the time of duration of AIM. This synergism takes one month become notable. TCM induced augmentation of dopamine receptor D2 expression and increase of its affinity might be the possible mechanism, which could also contains the rise of VMAT2 mRNA expression.