Study On The Effect Of The Wee On Neurotoxicity Induced By Paraquat In Mice

In recent years,people's demand for crop yield and pest control has increased.The abuse of pesticides and herbicides,such as excessive use,poisoning,and eating by mistake,endangers the environmental ecosystem and people's life and health.Paraquat(PQ),1-1'-dimethyl-4-4'-bipyridine cation salt,is a fast non-selective herbicide which is formed by the pyridine,sodium metal and dimethyl sulfate.Because of its wide range of weeding and good effect,paraquat is known as the king of pesticides.However,paraquat is toxic to people and animals and often used for suicide.It can enter human body through mouth or be absorbed by skin.And after that,paraquat will spread to the whole body,pass through the blood-brain barrier,damage neurons and nervous system,causing neurotoxicity.Epidemiology indicated that long-term exposure to paraquat can increase the prevalence of neurodegenerative diseases such as Parkinson's disease.In addition,paraquat is often used as a modelling drug of Parkinson's disease in experimental mice.Because the mechanism of paraquat neurotoxicity is not clear,so far,the specific antidote of paraquat has not been developed,which results in a very high lethality of paraquat.Therefore,the study of paraquat's neurotoxicity and treatment has prominent science significance and society value.Eucommia ulmoides(EU),also known as kapok and shisixian,is a precious Chinese medicinal material,which has the effects of nourishing liver and kidney,strengthening tendon and bones.The water extract of Eucommia ulmoides contains a variety of components,such as chlorogenic acid,lignin,flavonoids and iridoids,etc.It also has a good effect in lowering blood pressure,blood lipids,anti-osteoporosis,antibacterial and antiviral.However,so far,it is not known whether Eucommia ulmoides can treat the neurotoxicity caused by paraquat.In the present study,a model of paraquat poisoning in mice was established at first,and then the mice were treated with the water extract of Eucommia ulmoides Oliv.Bark(WEE)or same volume of saline solution.Using a series of techniques and methods such as Morris water maze,Masson staining,immunofluorescence staining,Brd U labeling,Western blotting and laser confocal observation,etc,we researched the neurotoxicity of paraquat to different brain regions of mice and the protective effect of water extract of Eucommia ulmoides Oliv.Bark on them.The results are as follows:(1)After the paraquat invaded,the learning and memory ability of the mice was significantly reduced.However,the mice's cognitive dysfunction caused by paraquat can be alleviated by taking water extract of Eucommia ulmoides Oliv.Bark.Moreover,Paraquat induced inflammation,hemorrhage,fibrosis and other symptoms in the lungs of mice.After the treatment of the water extract of Eucommia ulmoides Oliv.Bark,the lung damage of mice induced by paraquat was significantly improved,and the symptoms of hemorrhage and inflammation were alleviated.(2)After the mice exposed to paraquat,the number of proliferating cells,intermediate neurons and glial cells in the hippocampus changed significantly.However,the number of those cells can be significantly improved by taking water extract of Eucommia ulmoides Oliv.Bark.(3)After paraquat attacked,the expression of synaptic related proteins such as spinophilin,synaptophysin and PSD95 in the hippocampus of mice was abnormal.After taking the water extract of Eucommia ulmoides Oliv.Bark,the expression level of these synaptic related proteins tended to be normal.(4)The inflammation and apoptotic proteins such as NF-?B,ERK,p38 and caspase-3 were abnormal in the hippocampus of paraquat induced model mice.After taking the water extract of Eucommia ulmoides Oliv.Bark,the abnormalities of those proteins were recovered in varying degrees.(5)After the attacked of paraquat,the study focused on the brain stem and striatum area of mice.The results showed that the dopaminergic neurons in this area died,and the expression of dopaminergic secretion related proteins such as TH,TPH2 and CHAT were abnormal.After the treatment of the water extract of Eucommia ulmoides Oliv.Bark,the number of dopaminergic neurons increased significantly,and the expression level of related proteins was also saved.In conclusion,it is the first time that therapeutic effect of the water extract of Eucommia ulmoides Oliv.Bark on paraquat induced neurotoxicity was founded.