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Study Of The Protective Effect Of Edaravone On Paraquat Poisoning

Posted on:2013-09-05Degree:MasterType:Thesis
Country:ChinaCandidate:P B HuFull Text:PDF
GTID:2234330374981958Subject:Public Health
Abstract/Summary:PDF Full Text Request
Objective:to study the protective effect of edaravone on paraquat poisoning, and to explore its possible protective mechanisms.Methods:1. through clinical experimental study, the effect and its clinical significance of hs-CRP induced by edaravone on acute paraquat poisoning and the relationship between the effect of hs-CRP and the severity and prognosis of poisoning were observed, acute paraquat poisoning patients were divided into routine treatment group (the control group) and edaravone treatment group (referred to as the treatment group), in addition to the control group, patients in the treatment group were divided into MODS group and MODS group, on the day of admission and treatment after3th,7th,14th,21th days respectively extracts the peripheral venous blood hs-CRP level detection.2Establishment of paraquat (Paraquat PQ) induced by Parkinson’s disease (Parkinson’s disease PD) mouse model, observation of edaravone on paraquat-induced dopaminergic cells apoptosis.8weeks of age as a selection of110C57BL/6mice were randomly divided into control group, edaravone control group, paraquat group, edaravone protected group, except for the negative control group and edaravone control group, each group according to the lOmg/kg giving paraquat by intraperitoneal injection of saline, negative control group, edaravone protective measures, observation of mouse behavioral changes, whether Parkinson disease symptoms,8weeks after the mice were killed and taken out of brain tissue, HE staining was used to observe the changes of mesencephalic substantia nigra neurons, using immunohistochemical determination of Caspase-3expression, application of flow cytometry in different groups of mice brain cell apoptosis. The results obtained using the analysis of variance was used for statistical analysis. Results:1clinical experimental study showed:two groups of patients before treatment hs-CRP level had no significant difference (P>0.05); treatment of3,7,14,21days, two groups of patients with hs-CRP were significantly higher, differences were statistically significant (P<0.01); but no significant increase of edaravone in treatment group (P<0.01), two groups of patients in MODS group and MODS group hs-CRP level had a significant difference (P<0.01).2(1):Animal experimental study of behavioral change:compared with the negative control group, paraquat noticeable tremor, the action reduced and slowed Parkinson like symptoms.(2) pathological changes in brain tissue:negative control group and edaravone controls dopaminergic neurons distribution, morphological mostly normal; paraquat group showed dopaminergic neurons significantly reduced quantity, reduced the density, could be found in massive apoptosis, necrosis of neurons, possibly due to paraquat on midbrain dopaminergic neurons had certain destruction effect of paraquat group; and comparison of edaravone in the treatment group of dopaminergic cell volume reduction was not obvious, with a small quantity of apoptosis, necrosis of neurons, indicated that edaravone could prevent the degeneration of dopaminergic neurons lost to a certain extent.(3) immunohistochemical experiments:Paraquat group of mesencephalic substantia nigra compacta Caspase-3positive cells ratio compared with the negative control group and edaravone significantly increased (P<0.01), and that this activation may be edaravone suppressed, and paraquat groups compared, edaravone group of Caspase-3positive cells ratio lowered, the difference was statistically significant (P<0.01).(4) apoptosis results showed:compared with the negative control group of mice brain cell apoptosis rate and that of control group, edaravone cerebral cell apoptosis rate showed no significant difference (P>0.05), paraquat model mice brain cell apoptosis rate increased obviously, the difference was statistically significant (P<0.01), edaravone in the treatment of mice brain cell apoptosis rate of rise, difference had statistical significance (P<0.01); with paraquat than in model group, edaravone in the treatment of mice brain cell apoptosis rate decreased, the difference was statistically significant (P<0.01) Conclusions:1. hs-CRP can be used as patients with paraquat poisoning severity of illness observation indexes, serum hs-CRP levels and intoxication after MODS has a close relationship, edaravone can reduce the hs-CRP level in patients with acute paraquat poisoning, acute paraquat poisoning with obvious therapeutic effect.2. paraquat induced C57BL/6mice appear like Parkinson disease symptoms, the mesencephalic substantia nigra dopaminergic neurons decrease in number, edaravone induced by paraquat in PD mice has a protective effect, can reduce the acute paraquat poisoning caused by diffuse brain injury with edaravone, probably through inhibition of paraquat substantia nigra induced by DA neurons apoptosis and play a protective role, its mechanisms need to be further discussed.
Keywords/Search Tags:edaravone, paraquat, high sensitive C-reactive protein, Parkinson’s disease, DA neurons, cell apoptosis
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