对乙酰氨基酚致小鼠肝损伤早期血清苹果酸脱氢酶和嘌呤核苷磷酸化酶的变化

发布时间：2018-04-23 12:10

本文选题：对乙酰氨基酚 + 肝损伤　；参考：《毒理学杂志》2015年01期

【摘要】：目的探讨血清苹果酸脱氢酶(MDH)和嘌呤核苷磷酸化酶(PNP)对肝损伤早期诊断的应用价值。方法 C57小鼠随机分为对照组、低剂量组、中剂量组和高剂量组,各剂量组分别灌胃给予对乙酰氨基酚(APAP)200、350和500 mg/kg,对照组给予生理盐水。于给药后不同时间点(3、6、12和24 h)采集血清,用全自动生化分析仪测定血清谷丙转氨酶(ALT)的水平,紫外分光光度计测定血清MDH的水平,ELISA测定血清PNP的水平。解剖后取肝脏计算肝指数,并进行HE染色,观察肝组织病理形态学变化。结果与对照组同时间点相比,给APAP后3 h,各剂量组MDH均显著升高(P0.05或P0.01),PNP在中剂量组及高剂量组显著升高(P0.05或P0.01),ALT则无明显变化;给APAP后6 h,各剂量组ALT、MDH和PNP均明显升高(P0.05或P0.01);给APAP后12 h,中剂量组及高剂量组ALT和MDH显著升高(P0.01),PNP在各剂量组均显著升高(P0.01);给APAP后24 h,各指标水平均有所下降,和对照组同时间点相比,ALT、MDH和PNP仅在高剂量组有显著性差异(P0.01)。与对照组相比,各时间点高剂量组肝指数均显著升高(P0.05或P0.01),显微镜下肝组织病理切片可见明显的肝细胞脂肪变性,高剂量组出现水肿。结论 MDH和PNP在肝损伤早期ALT没有发生明显变化时就显著升高,具有较好的灵敏性,且变化趋势与ALT相同,与病理结果一致,可以作为APAP致肝损伤早期的生物学标志。
[Abstract]:Objective to investigate the value of serum malate dehydrogenase (MDH) and purine nucleoside phosphorylase (PNPs) in the early diagnosis of liver injury. Methods C57 mice were randomly divided into three groups: control group, low dose group, middle dose group and high dose group. Each dose group was given paracetamol APP 200350 and 500 mg / kg, and the control group was given normal saline. Serum samples were collected at different time points at 12 and 24 hours after administration. Serum alanine aminotransferase (alt) levels were measured by automatic biochemical analyzer. Serum MDH levels were measured by UV spectrophotometer and serum PNP levels were determined by Elisa. After dissection, the liver index was calculated and HE staining was performed to observe the histopathologic changes of the liver. Results compared with the control group at the same time point, at 3 h after APAP, the MDH of each dose group was significantly higher than that of the control group (P 0.05 or P 0.01), but there was no significant difference between the middle dose group and the high dose group (P 0.05 or P 0.01). At 6 hours after APAP, the levels of alt MDH and PNP were significantly increased in each dose group (P 0.05 or P 0.01), and at 12 h after APAP, ALT and MDH in middle dose group and high dose group were significantly increased in all dose groups, and the levels of ALT and MDH were decreased at 24 h after APAP administration, and the levels of ALT and MDH in the middle dose group and high dose group were significantly higher than those in the control group at 24 h after APAP administration, the levels of ALT and MDH in the middle dose group were significantly higher than those in the control group. Compared with the control group, MDH and PNP only showed significant difference in high dose group (P 0.01). Compared with the control group, the liver index of the high dose group was significantly higher than that of the control group (P 0.05 or P 0.01). Steatosis of liver cells could be seen in pathological sections of liver tissue under microscope, and edema appeared in the high dose group. Conclusion MDH and PNP increased significantly at the early stage of liver injury, and had good sensitivity, and the change trend was the same as that of ALT, which could be used as a biological marker in the early stage of liver injury caused by APAP.
【作者单位】：首都医科大学附属北京中医医院检验科;军事医学科学院疾病预防控制所毒理学评价研究中心;
【基金】：重大新药创制科技重大专项(2012ZX09J12203-002)
【分类号】：R994

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