药物对急性羰基镍中毒大鼠肝细胞损伤的治疗作用

目的 评价药物对急性羰基镍中毒大鼠肝细胞DNA损伤的影响.方法 将SD大鼠分为正常对照组(10只)、染毒组(10只),治疗组为甲泼尼龙组(20mg/kg)、二乙基二硫代氨基甲酸钠(DDC)组(100mg/kg)、亚硒酸钠组(10 μmol/kg)、参附回阳汤组(0.25ml)、甲泼尼龙组(20mg/kg)+DDC(100mg/kg)组,每组40只.除正常对照组外,其余各组大鼠静态吸入250mg/m3羰基镍染毒30min,分别于染毒后4 h和30 h给药,3 d和7 d取材,每组各10只,采用单细胞凝胶电泳试验检测药物对肝细胞DNA损伤的影响,电子显微镜观察大鼠肝细胞超微结构改变.结果 与染毒组比较,甲泼尼龙组、DDC组、亚硒酸钠组、参附回阳汤组及甲泼尼龙+DDC组染毒4 h和30 h给药,观察3、7 d时彗星尾长均减小,差异有统计学意义(P＜0.05);与正常对照组比较,亚硒酸钠组、参附回阳汤组4 h给药及DDC组、亚硒酸钠组、参附回阳汤组及甲泼尼龙+DDC组30 h给药,观察3 d时彗星尾长均明显增大,差异有统计学意义(P＜0.05或P＜0.01).除甲泼尼龙组4 h给药,观察7 d时彗星尾长差异无统计学意义(P＞0.05)外,其他各组4 h、30 h给药,观察7 d时彗星尾长均明显增大,差异有统计学意义(P＜0.05,P＜0.01).与染毒组比较,甲泼尼龙组、DDC组、亚硒酸钠组、参附回阳汤组及甲泼尼龙+DDC组4 h和30 h给药,观察3、7 d时彗星Olive尾距均减小,差异有统计学意义(P＜0.05,P＜0.01);与正常对照组比较,4h和30 h给药亚硒酸钠组、参附回阳汤组(观察3、7 d)及DDC组(观察7 d),30 h给药DDC组(观察3d)和甲泼尼龙+DDC组(观察7 d)时彗星Olive尾距明显增大,差异有统计学意义(P＜0.05或P＜0.01).肝细胞超微结构观察显示,与染毒组比较,甲泼尼龙组、DDC组和甲泼尼龙+DDC组4 h给药,观察3 d时胞质内细胞器及细胞核损伤已基本恢复到接近正常水平.结论 甲泼尼龙、DDC和甲泼尼龙+DDC具有较强促进急性羰基镍中毒后大鼠肝细胞损伤的修复作用,且早期治疗效果明显优于晚期.

Abstract：

Objective To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning. Methods In present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats),20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 μmol/kg sodium selenite group (40 rats),0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats ). All rats except for control group inhaled passively 250 mg/m3 carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope. Results Compared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4h or 30h and tested on the 3rd or 7th day after exposure decreased significantly (P＜0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite,shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P＜0.05 or P＜0.01 ), when tested on the 3rd day after exposure. Except from methylprednisolonesub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P＜0.05).Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P＜0.05 or P＜0.01 ). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4h or 30h and tested on the 7th day after exposure, DDC group administrated at 30 h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P＜0.05 or P＜0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone,DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels. Conclusion The results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.

The curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning

Objective To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning. Methods In present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats),20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 μmol/kg sodium selenite group (40 rats),0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats ). All rats except for control group inhaled passively 250 mg/m3 carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope. Results Compared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4h or 30h and tested on the 3rd or 7th day after exposure decreased significantly (P＜0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite,shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P＜0.05 or P＜0.01 ), when tested on the 3rd day after exposure. Except from methylprednisolonesub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P＜0.05).Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P＜0.05 or P＜0.01 ). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4h or 30h and tested on the 7th day after exposure, DDC group administrated at 30 h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P＜0.05 or P＜0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone,DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels. Conclusion The results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.