依达拉奉对百草枯中毒大鼠急性肺损伤治疗作用

The therapeutic effect of edravone on acute lung injury induced by paraquat in rats

目的研究依达拉奉对百草枯中毒急性肺组织损伤的治疗作用及可能机制。方法将96只雄性SD大鼠随机分为对照组(Con组)、模型组(Mod组)、依达拉奉治疗组(ED组)和地塞米松治疗组(Dex组),每组再根据染毒时间分为6h、24h、48h和72h等4个亚组,每组6只。采用腹腔注射20%百草枯溶液(25mg/kg)制备百草枯中毒急性肺损伤模型,Con组腹腔注射等容积生理盐水。染毒后1h开始,ED组和Dex组分别给予腹腔注射依达拉奉(3mg/kg)和地塞米松(3mg/kg),2次/日,Con组和Mod组给予等容积生理盐水。分别在染毒后6h、24h、48h和72h,观察大鼠一般状况变化,然后处死大鼠,经心脏采集血液标本检测血清SOD活性和MDA含量,并行HE染色观察肺组织病理变化。结果与Con组比较,Mod组、ED组及Dex组各时间点血清SOD活性明显下降(P<0.05或P<0.01),血清MDA水平均明显增加(P<0.01),肺组织病理示急性肺损伤改变,炎症细胞浸润,肺泡萎缩塌陷,甚至结构消失,且随时间进展加重;与Mod组相比,ED组和Dex组血清SOD活性明显上升(P<0.05或P<0.01),血清MDA含量明显下降(P<0.05或P<0.01),肺组织病理改变明显减轻;而ED组和Dex组间差异无统计学意义(P>0.05)。结论依达拉奉和地塞米松对百草枯中毒引起的急性肺损伤均有治疗作用,其治疗作用和减轻自由基损伤有关。

Objective To investigate the probable mechanism of edaravone in the process of protecting acute lung injury induced by paraquat poisoning.Methods 96 male SD rats were divided into the control group（Con group）,the model group（Mod group）,the edaravone treatment group（ED group）,the dexamethasone treatment group（Dex group）,each group were divided into four subgroups of 6h,24h,48h and 72h（n=6）.The acute lung injury model induced by paraquat poisoning was produced by intraperitoneal injection 20% paraquat solution with the dose of 25mg/kg,and the rats in control group were given normal saline solution with the same volume.One hour after the administration,rats in ED group and Dex group were given edaravone（3mg/kg） and dexamethasone（3mg/kg）,twice a day while the Con group and the Mod group were given normal saline solution with the same volume.6h,24h,48h and 72h after the administration,observe the changes of rats＇ behaviors;then killed the rats and collected blood samples by heart to measure the content of serum MDA and the activity of SOD,and observed the pathology of lung tissue by HE staining.Results Compared to the Con group,the activity of SOD had increased greatly（P0.05 or P0.01） and the content of MDA in serum bloods had significantly decreased（P0.01） in the Mod group,ED group and Dex group,the pathology of Lung tissue shows acute lung injury,inflammatory cells infiltrating,the alveolar atrophied and collapsed even structure disappeared,and gradually aggravated over the time,compared to the Mod group,the activity of SOD had increased greatly（P0.05 or P0.01） and the content of MDA in serum bloods had significantly decreased（P0.05 or P0.01） in the ED group and Dex group;the pathological change of the lung tissue significantly reduced;however,there were no significant difference between the ED group and the Dex group（P0.05）.Conclusion Both edaravone and dexamethasone have therapeutic effects on the acute lung injury induced by paraquat poisoning and the mechanism may be associated with the ruduction of the radical injury.