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大鼠肾脏GSH和SOD酶评价急性羰基镍中毒的药效观察

Intervention effects of drugs on GSH and SOD enzyme activity of rats kidney acutely poisoned by nickel carbonyl
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摘要 目的评价多种药物对急性羰基镍中毒大鼠肾组织谷胱甘肽(GSH)和超氧化物歧化酶(SOD)活力的干预效果。方法于2019年1月,选择250只SPF级SD雄性大鼠按随机数字表法随机分为正常对照组(10只)、染毒对照组(40只)及治疗组(200只),其中治疗组分为甲泼尼龙(20 mg/kg)组、二乙基二硫氨基甲酸钠(DDC)(100 mg/kg)组、亚硒酸钠(10μmol/kg)组、回阳注射液(0.25 ml)组、甲泼尼龙(20 mg/kg)+DDC(100 mg/kg)组,每组各40只。除正常对照组外,其余各组大鼠静态吸入羰基镍250 mg/m3染毒30 min,分别于染毒后4 h和30 h对各治疗组大鼠腹腔注射相应药物,连续给药3 d或7 d后取肾组织,每组各10只。采用酶联免疫吸附实验测定肾组织GSH和SOD活力,透射电镜观察大鼠肾组织超微结构变化。结果与正常对照组比较,染毒4 h或30 h后3 d或7 d染毒对照组肾组织GSH、SOD活力均明显降低,差异有统计学意义(P=0.000、0.031、0.001、0.033),肾近曲小管上皮细胞核明显固缩,胞质内溶酶体增生;与染毒对照组比较,染毒4 h后给药7 d甲泼尼龙+DDC组大鼠肾组织GSH和SOD活力明显增高,差异有统计学意义(P=0.022、0.000),甲泼尼龙组、甲泼尼龙+DDC组给药7 d大鼠肾组织的GSH和SOD活力明显高于给药3 d者,差异有统计学意义(P=0.020、0.017、0.018、0.033),电镜结果显示该两组的肾近曲小管上皮细胞核及胞质细胞器结构基本恢复正常组织水平。结论甲泼尼龙、甲泼尼龙+DDC对急性羰基镍中毒大鼠肾组织酶活力水平有明显修复作用,且用药时间长的治疗效果更好。 Objective To evaluate the intervention effect of various drugs on glutathione(GSH)and superoxide dismutase(SOD)enzyme activity of rats kidney with acute nickel carbonyl poisoning.Methods In January 2019,The 250 SPF male SD rats were randomly divided into normal control group(n=10),poisoned group(n=40)and treatment groups(n=200)according to the random number table method.And the treatment groups were divided into methylprednisolone group(20 mg/kg),DDC group(100 mg/kg),sodium selenite group(10μmol/kg),Shenfu huiyang decoction group(0.25 ml)and methylprednisolone combined with DDC group(100 mg/kg),with 40 mice in each group.Except for the normal control group,rats in the other groups were exposed to nickel carbonyl for 30 min,at 4 h and 30 h after exposure,the rats in each treatment group were intraperitoneally injected with corresponding drugs,and kidney tissues were collected 3 d and 7 d after administration,with 10 mice in each group.The activities of GSH and SOD in kidney were measured by enzyme-linked immunosorbent assay,and using electron microscopy observe ultrastructure changes.Results Compared to the control group,the activities of GSH and SOD enzyme of poisoned group were significantly decreased at 3 d or 7 d after 4 h or 30 h exposure,and the difference was statistically significant(P=0.000,0.031,0.001,0.033),the epithelial nuclei of proximal convoluted tubules were pyknosis and lysosome hyperplasia in the cytoplasm.And compared to poisoned group,the activities of GSH and SOD enzyme of methylprednisolone+DDC group were significantly increased at treatment with 7 d after 4 h exposure,the difference was statistically significant(P=0.022,0.000),and the activities of GSH and SOD enzyme of methylprednisolone and enzyme of methylprednisolone+DDC group were significantly higher at 7 days than at 3 days,the difference was statistically significant(P=0.020,0.017,0.018,0.033).The results of electron microscopy showed that the cell nuclei and cytoplasmic organelles of proximal convolute tubule were almost restored to normal tissue level of both methylprednisolone group and methylprednisolone+DDC group.Conclusion The methylprednisolone and methylprednisolone+DDC have obvious repair effect on renal enzyme activity level of rats with acute nickel carbonyl poisoning,and the treatment effect is better for a long time of medication.
作者 马玲玲 张德生 马国煜 张小培 吴喜江 程宁 Ma Lingling;Zhang Desheng;Ma Guoyu;Zhang Xiaopei;Wu Xijiang;Cheng Ning(Key Lab of Preclinical Studies for New Drugs of Gansu Province,Lanzhou University,Gansu 730000,China;Workers Hospital,Jinchuan Company,Gansu 730000,China;Nickel Cobalt Industrial Health Research Institute,Jinchuan Company,Gansu 730000,China)
出处 《中华劳动卫生职业病杂志》 CAS CSCD 北大核心 2022年第12期888-892,共5页 Chinese Journal of Industrial Hygiene and Occupational Diseases
基金 兰州大学与金川集团有限公司产学研项目 (金科综2011-18、2013-18)。
关键词 羰基镍 谷胱甘肽 超氧化物歧化酶 甲泼尼龙 二乙基二硫氨基甲酸钠 Nickel carbonyl Glutathione activity Superoxide dismutase activity Methylprednisolone Diethyldithiocarbamate
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