Establishment Of PD Rat Model By Injecting Taclo Sterically And Directionally Into Striatum

BackgroundTrichloroethylene(TCE) is a kind of chlorinated organic compounds which is widely used as degreasing agent and extraction solvent because of its high lipid solubility and good solubility in organic solvents.It is also used for the preparation of narcotic and abortion drugs in medicine.In2008,Professor Guoying Bing and Don Gash from Kentucky university accidentally discovered that people who expose himself to low concentrations of TCE for a long time will have neurological impairment. People show symptoms of bradykinesia and uncoordinated movements some of them show typical symptoms of Parkinson’s disease. Then Professor Guoying Bing fed rats with TCE which successfully build PD rat model and he found the degeneration of nigrostriatal system and damage of dopaminergic neurons in substantia nigra.TCE metabolizes in two ways in human body including the cytochrome P450(CYP450) oxidation pathway and glutathione (GSH) combination way.Taclo is one of the metabolic products of TCE and it is produced inCYP450oxidation pathways.Maybe Taclo plays an important role in the pathogenesis of TCE because of its similar molecular structure to MPTP which has been proved to cause Parkinson’s disease.Object To observe the destructive effects of Taclo on the dopaminergic neurons in the substantia nigra after striatal injection and establish PD rat model for further research.Methods Sixty male wistar rats were randomly divided into polyethylene glycol(PEG)and Taclo group,30in each group.Apomorphine-induced rotation was observed two weeks after injection and rats’trajectory was recorded by the automatic video tracking system.The rats were sacrificed one month later and tyrosine hydroxylase(TH) immunochemistry was conducted.High Performance Liquid Chromatograph(HPLC) and Western Blotting was also conducted as well.Results24rats constantly rotated to the left side at a speed above210r/30min in Taclo group.The trajectory became sparse in these rats.The results of immunochemistry showed that the number of TH-positive neurons in right substantia nigra of rats in Taclo group decreased than those in left substantia nigra and bilateral substantia nigra in PEG group(P<0.05). The results of HPLC showed that dopamine in right substantia nigra of rats in Taclo group decreased while Western Blotting showed that capase-3and cox-2increased.24rats can be regarded as successful PD rat models.Conclusion The degeneration of dopaminergic neurons can be observed and PD rat models can be established by injecting Taclo sterically and directionally into striatum.