CAJ | 학술논문

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. 目的評價藥物對急性羰基鎳中毒大鼠肝細胞DNA損傷的影響.方法將SD大鼠分為正常對照組(10隻)、染毒組(10隻),治療組為甲潑尼龍組(20mg/kg)、二乙基二硫代氨基甲痠鈉(DDC)組(100mg/kg)、亞硒痠鈉組(10 μmol/kg)、參附迴暘湯組(0.25ml)、甲潑尼龍組(20mg/kg)+DDC(100mg/kg)組,每組40隻.除正常對照組外,其餘各組大鼠靜態吸入250mg/m3羰基鎳染毒30min,分彆于染毒後4 h和30 h給藥,3 d和7 d取材,每組各10隻,採用單細胞凝膠電泳試驗檢測藥物對肝細胞DNA損傷的影響,電子顯微鏡觀察大鼠肝細胞超微結構改變.結果與染毒組比較,甲潑尼龍組、DDC組、亞硒痠鈉組、參附迴暘湯組及甲潑尼龍+DDC組染毒4 h和30 h給藥,觀察3、7 d時彗星尾長均減小,差異有統計學意義(P＜0.05);與正常對照組比較,亞硒痠鈉組、參附迴暘湯組4 h給藥及DDC組、亞硒痠鈉組、參附迴暘湯組及甲潑尼龍+DDC組30 h給藥,觀察3 d時彗星尾長均明顯增大,差異有統計學意義(P＜0.05或P＜0.01).除甲潑尼龍組4 h給藥,觀察7 d時彗星尾長差異無統計學意義(P＞0.05)外,其他各組4 h、30 h給藥,觀察7 d時彗星尾長均明顯增大,差異有統計學意義(P＜0.05,P＜0.01).與染毒組比較,甲潑尼龍組、DDC組、亞硒痠鈉組、參附迴暘湯組及甲潑尼龍+DDC組4 h和30 h給藥,觀察3、7 d時彗星Olive尾距均減小,差異有統計學意義(P＜0.05,P＜0.01);與正常對照組比較,4h和30 h給藥亞硒痠鈉組、參附迴暘湯組(觀察3、7 d)及DDC組(觀察7 d),30 h給藥DDC組(觀察3d)和甲潑尼龍+DDC組(觀察7 d)時彗星Olive尾距明顯增大,差異有統計學意義(P＜0.05或P＜0.01).肝細胞超微結構觀察顯示,與染毒組比較,甲潑尼龍組、DDC組和甲潑尼龍+DDC組4 h給藥,觀察3 d時胞質內細胞器及細胞覈損傷已基本恢複到接近正常水平.結論甲潑尼龍、DDC和甲潑尼龍+DDC具有較彊促進急性羰基鎳中毒後大鼠肝細胞損傷的脩複作用,且早期治療效果明顯優于晚期.
목적 평개약물대급성탄기얼중독대서간세포DNA손상적영향.방법 장SD대서분위정상대조조(10지)、염독조(10지),치료조위갑발니룡조(20mg/kg)、이을기이류대안기갑산납(DDC)조(100mg/kg)、아서산납조(10 μmol/kg)、삼부회양탕조(0.25ml)、갑발니룡조(20mg/kg)+DDC(100mg/kg)조,매조40지.제정상대조조외,기여각조대서정태흡입250mg/m3탄기얼염독30min,분별우염독후4 h화30 h급약,3 d화7 d취재,매조각10지,채용단세포응효전영시험검측약물대간세포DNA손상적영향,전자현미경관찰대서간세포초미결구개변.결과 여염독조비교,갑발니룡조、DDC조、아서산납조、삼부회양탕조급갑발니룡+DDC조염독4 h화30 h급약,관찰3、7 d시혜성미장균감소,차이유통계학의의(P＜0.05);여정상대조조비교,아서산납조、삼부회양탕조4 h급약급DDC조、아서산납조、삼부회양탕조급갑발니룡+DDC조30 h급약,관찰3 d시혜성미장균명현증대,차이유통계학의의(P＜0.05혹P＜0.01).제갑발니룡조4 h급약,관찰7 d시혜성미장차이무통계학의의(P＞0.05)외,기타각조4 h、30 h급약,관찰7 d시혜성미장균명현증대,차이유통계학의의(P＜0.05,P＜0.01).여염독조비교,갑발니룡조、DDC조、아서산납조、삼부회양탕조급갑발니룡+DDC조4 h화30 h급약,관찰3、7 d시혜성Olive미거균감소,차이유통계학의의(P＜0.05,P＜0.01);여정상대조조비교,4h화30 h급약아서산납조、삼부회양탕조(관찰3、7 d)급DDC조(관찰7 d),30 h급약DDC조(관찰3d)화갑발니룡+DDC조(관찰7 d)시혜성Olive미거명현증대,차이유통계학의의(P＜0.05혹P＜0.01).간세포초미결구관찰현시,여염독조비교,갑발니룡조、DDC조화갑발니룡+DDC조4 h급약,관찰3 d시포질내세포기급세포핵손상이기본회복도접근정상수평.결론 갑발니룡、DDC화갑발니룡+DDC구유교강촉진급성탄기얼중독후대서간세포손상적수복작용,차조기치료효과명현우우만기.
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.