多种药物对急性羰基镍中毒大鼠肺组织和细胞损伤的治疗作用

Therapeutic effect of drugs on damage of tissues and cells in rats with acute carbonyl nickel poisoning

目的评价多种药物对急性羰基镍中毒大鼠肺细胞DNA损伤的治疗作用以及形态学变化。方法 SD大鼠静态吸入羰基镍250mg·m-3染毒30min,分别在4h和30h后ip给予甲泼尼龙、扎西他滨(DDC)、亚硒酸钠、参附回阳汤和甲泼尼龙+DDC。在3d和7d后取肺细胞,单细胞凝胶电泳实验检测肺细胞DNA损伤,并通过光学显微镜和透视电镜观察大鼠肺肺组织病理变化和细胞超微结构改变。结果与染毒对照组比较,甲泼尼龙、DDC、亚硒酸钠、参附回阳汤及甲泼尼龙+DDC对急性羰基镍中毒后大鼠肺细胞DNA损伤均有明显修复作用(P<0.05),肺组织渗出性改变明显减轻,线粒体损伤明显修复。与正常对照组比较,甲泼尼龙和甲泼尼龙+DDC治疗后DNA损伤和线粒体等细胞器损伤修复已接近正常水平,且4h给药各组的治疗作用好于30h给药(P<0.05)。结论甲泼尼龙和甲泼尼龙+DDC组对急性羰基镍中毒后大鼠肺组织细胞损伤有明显修复作用,早期治疗效果明显优于晚期。

OBJECTIVE To assess the treatment efficacy and morphological changes of screening drugs on DNA damage in rat lung cells affected by acute carbonyl nickel poisoning.METHODSSD rats passively inhaled carbonyl nickel 250 mg·m-3 for 30 min,separated into prednisolone,sodium diethyl dithiocarbamate(DDC),sodium selenite,Shenfuhuiyangtang or methylprednisolone combined with DDC at 4 or 30 h after exposure.Lung cells were examined by single cell gel electrophoresis(SCGE) 3 and 7 d after exposure to examine treatment efficacy for lung cell DNA damage,pathological changes in lung tissue and changes in lung cell ultra microstructure.RESULTSCompared to carbonyl nickel group,methylprednisolone,DDC,sodium selenite,Shenfuhuiyangtang and methylprednisolone combined with DDC exhibited therapeutic effects for rat lung cells exposed to acute carbonyl nickel poisoning(P<0.05),with significantly reduced lung tissue inflammation and restoration of damaged mitochondria.Compared to the control group,repair of damage to DNA,mitochondria and other organelles by methylprednisolone and methylprednisolone plus DDC approached pre-exposure levels.Treatment efficacy was much better at 4 h after exposure than after 30 h(P<0.05).CONCLUSION Methylprednisolone and methylprednisolone combined with DDC exhibit significant restorative effects for rat lung tissue cells affected by acute carbonyl nickel poisoning,with earlier treatment more effective than later treatment.