The Efficacy Of Ctxn From Naja Naja Atra Venom For Pd Models Induced By 6-ohda

Objective1,To explore the feasibility that dyskinesia model in rats can be made by complete damage to substantia nigra dopaminergic neurons.2,To search the efficacy of CTXn from Naja naja atra venom for Parkinson's disease(PD)models induced by 6-OHDA.Methods1,To make rat models with substantia nigra completely injured by the use of large doses of 6-OHDA and moderately injured by medium doses. To assess rats motor function by Rota Rod Test and evaluate rats forelimb function with Cylinder Test. To evaluate rat behavior with abnormal involuntary movement (AIM) score after levodopa (L-DOPA) administration. And to detect TH cells by immunohistochemistry and striatum dopamine levels by High Performance Liquid Chromatography (HPLC).2,To establish the models of Parkinson's disease dyskinesia through complete damage to substantia nigra dopaminergic neurons with high-dose 6-OHDA, then evaluate motor function of the models through Rota Rod test and compare the abnormal involuntary movement (AIM) score induced by levodopa(L-DOPA) after administrating CTXn(saline for placebo control).3,To establish the models of Parkinson's disease through moderate damage to substantia nigra dopaminergic neurons with medium-dose 6-OHDA, then to detect the effect of nicotine with Rota Rod test and APO in these models established above which were injected CTXn before subcutaneous injection of nicotine. 4,To compare the motor function with Rota Rod test and the rotational behavior induced by APO between acute CTXn intervention and chronic in PD models, then to observe the TH positive cells in substantia nigra and dopamine D2 receptor positive cells in striatum by immunohistochemistry. The control were treated with placebo and then treated with the same steps mentioned above.Results1. The success rate of animal model made by high-dose 6-OHDA was 71%, and mortality rate was 7%.2. In the rat models whose substantia nigras were destroyed completely, the running time on Rota-Rod Treadmills drop to 55.3% of the control, and the proportion of use of ipsilateral paw in the cylinder test drop to 19.6%; The rat model with substantia nigra completely injured showed AIM behavior when first administration of L-DOPA or APO,and the AIM score increase with increasing doses of L-DOPA. In the rats with substantia nigras destroyed completely, more than 98% TH-positive cells in the ipsilateral substantia nigras are lost, and the ipsilateral striatum DA level drop to 0.94% of the contralateral.3,For the rat models of dyskinesia, acute intervention of CTXn reduce the AIM score induced by L-DOPA, and do not decrease the motor function of the models.4,For the PD rat models, acute intervention of nicotine decrease the motor function of the models and CTXn take no effect on the role of nicotine, and acute intervention of CTXn decrease the motor function in Rota Rod test and rotational behavior induced by APO.5,For the PD rat models, chronic intervention of CTXn increase the motor function in Rota Rod test, and the dopamine D2 receptor expression increase in ipsilateral striatum, but the TH positive cells in substantia nigra and ChAT positive cells in striatum have no change in expression.Conclusions:1. It is feasible to make PD dyskinesia models by damaging substantia nigra completely with high-dose 6-OHDA.2. The CTXn from Naja naja atra venom may attenuate the AIM behavior induced by L-Dopa in the dyskinesia models.3. The CTXn may increase the expression of dopa D2 receptor in PD models.