Research About Toxicity Of Levodopa On Parkinsonian Nerve Cells And Neuroprotective Factors

Objective:Parkinson' disease (PD) is the main neurodegenerative disorder that influences the middle age and old people, its cause is still not clear. Therefore, there isn't treatment measure aiming at the cause of disease currently. As the most valid medicine, levodopa can alleviate symptom simply, and can't obstruct and decelerate the progress of PD, contrarily levodopa can accelerate apoptosis and putrescence of dopamine neurons. Therefore, exploring the etiology and valid medicine can improve mankind's health level significantly.PD is chronic and progressive neurodegenerative disease, which is diagnosed mainly depending on the clinic performance without particularity. Thus, the effective rate of diagnosis is about 75%～80%,and while appear clinical symptom, death of dopamine neurons have exceeded 80%. And, put forward with the research of nerve nourishment factor along with the neuroprotective strategy, the patient of PD need more and more to be examined and given neuroprotective treatment in early days. It is important to improve the patient's prognosis and the living quality.In this study, we directive injected 6-OHDA into the right striatum of rat to prepare the hemilateral model of PD. Behavior, immunohistochemical stainin and so on were performed in order to probe into the relation of the immunology, apoptosis and etiology of PD.Methods:After injecting 6-OHDA into the right striatum of rat for 2 weeks, we obtained the hemi-lateral model of PD. The control group was set up by injecting isodose physiological saline as pseudo-operation rats. All the animals were divided into 6groups:control group,model group,madopar group,selegiline hydrochloride group,Chinese medicine chanfuning group and leigongtengduodai group. Each group has 6 rats. The control and model groups were treated with physiological saline for 30 days, and the rats in madopar group,selegiline hydrochloride group,Chinese medicine chanfuning group,leigongtengduodai group were separately treated with madopar, selegiline hydrochloride,Chinese medicine chanfuning, leigongtengduodai for 30 days. The rotational behavior was evaluated by recording the number of apomorphine-induced turns. We used caspase-3 and D2R immunohistochemical staining to investigate the numbers of positive neurons in SNc, striatum and hippocampus.Results:1. Madopar,selegiline hydrochloride,Chinese medicine chanfuning leigongtengduodai can ameliorate the rotational behavior of Parkonsonian rats, comparing with the control group, P< 0.01.2. D2R positive neurons in right SNc,striatum and hippocampus of the PD model group significantly decrease(P< 0.01). After being treated with selegiline hydrochloride,Chinese medicine chanfuning,leigongtengduodai, they can partly be restored.3. Caspase-3 positive neurons in right SNc, striatum and hippocamus of PD model group significantly increase(P< 0.01) and madopar group increase more than PD model group. The positive neurons of selegiline hydrochloride,Chinese medicine chanfuning,leigongtengduodai group is more few than PD model group.Conclusions:Although levodopa can ameliorate the symptom of PD obviously, it can promote the dopamine neurons injury via inducing apoptosis. Selective irreversible inhibitor of mono amine oxidase B(MAO-B), Chinese medicine chanfuning,leigongtengduodai can improve the rotational behavior of PD rats, restrain apoptosis, decrease injury of immunoflammatory reaction and protect dopamine neurons in SNc and striatum.