Experimental Studies On The Inhibition Of The Exogenous SOD In The Dopaminergic Neuron Apoptosis Induced By 6-OHDA In Rat Midbrain

Parkinson's disease (PD) is a common neurodegenerative disorder of central nervous system (CNS) related closely with ages, which mainly characterized by progressive loss of dopaminergic neurons in the nigrostriatal system. The major pathogenesises of PD include oxidative stress, mitochondria malfunction, endogenous toxin and descent of neurotrophic factor protection in the dopaminergic neurons. Oxidative stress has caused much more attention because of 1-1202, the oxidation metabolites of Dopamine and the other reactive oxygen specie s(ROS) ,which plays an important role in PD progress. However, 6-hydroxydopamine, a neurotoxin, can selectively destroy the dopaminergic nigrostraital pathway inducing a severe nerve cell loss in the pars compacta of the substantia nigra (SNc), and producing a chronic disfunction of SNc in neurology, biochemistry and the pathology,which are similar to the human idiopathic parkinsonism. In this study, 144 of adult male Sprague-Dawley (SD) rats were randomly divided into nine groups, including Normal, Saline Control,Lesion Group, Prevention Control and Prevention A, B, C, D,E Groups. 6-hydroxydopamine (iOl ig/6l tl) was injected into the right SNc through sereotaxic operation in Lesion Group. And physiological saline, instead of 6-OHDA (1O~Lg/6~~L1) , was injected in the same target in Saline Control. In Prevention Groups, exogenous SOD (9OIU/6It1) was injected at the different time, such as at 0-hour, one-hour before or after injection of 6-OHDA, seven-hour and twelve-hour after injecting 6-OHDA by the same method above, which were respectively named as Group A, B, C, D, E. 6-OHDA and Saline were injected into the right SNc at the same time in the Prevention Control.At 10 day after operation, the rats were injected with apomorphine in order to induce a special rotation in head-tail direction, which represents a successful model of PD . Total antioxidation ability, active oxygen, total-SOD and CuZn-SOD activity of midbrain were measured by test kit to define oxidative stress in midbrain. The changes of dopaminergic neurons and apoptosis in SNc were immunohistochemicaly studied with tyrosine hydroxylase (TH) and TUNEL (TdT-mediated biotinylated-dUTP nick end) method to respectively find the dopaminergic neurons apoptosis induced by 6-OHDA and the antagonistic action of the exogenous SOD. Results: 1. Praxiology observation: At 10 day after opera~tion, the rats presented the special rotation following intraperitoneal injection of apomorphine (0. 5mg/kg). The rotational speeds in Prevention Contral and Lesion Group were 187. 9?l9circle/30min, 166. 7?1 circle/30rnin respectively. The rotational speeds in Prevemtion Groups decreased with certain degree, especially in the Group B remarkablely (p