[1]苗玉发,康慧君,王 超,等.血清维生素D结合蛋白水平检测对大鼠肝毒性诊断的评价研究[J].现代检验医学杂志,2019,34(04):6-10.[doi:10.3969/j.issn.1671-7414.2019.04.002]
　MIAO Yu-fa,KANG Hui-jun,WANG Chao,et al.Evaluation of Serum Vitamin D Binding Protein Levels in the Diagnosis of Hepatotoxicity in Rats[J].Journal of Modern Laboratory Medicine,2019,34(04):6-10.[doi:10.3969/j.issn.1671-7414.2019.04.002]
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血清维生素D结合蛋白水平检测对大鼠肝毒性诊断的评价研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第34卷
期数:
2019年04期
页码:
6-10
栏目:
论著
出版日期:
2019-08-20

文章信息/Info

Title:
Evaluation of Serum Vitamin D Binding Protein Levels in the Diagnosis of Hepatotoxicity in Rats
文章编号:
1671-7414(2019)04-006-05
作者:
苗玉发; 康慧君; 王 超; 张河战
(中国食品药品检定研究院,药物非临床安全评价研究北京市重点实验室,北京 100176)
Author(s):
MIAO Yu-fa; KANG Hui-jun; WANG Chao; ZHANG He-zhan
(National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drug,Beijing 100176,China)
关键词:
维生素D结合蛋白;  肝功能;  肝毒性
分类号:
R-332
DOI:
10.3969/j.issn.1671-7414.2019.04.002
文献标志码:
A
摘要:
目的 评价血清维生素D结合蛋白(vitamin D binding protein,VDBP)用于大鼠肝毒性诊断的价值。方法 用酮康唑(ketoconazole,KTZ)、四氯化碳(carbon tetrachloride,CCl4)和对乙酰氨基酚(acetaminophen,APAP)在雄性大鼠中构建3种肝毒性模型,在不同时间点从腹腔大静脉采集外周血,3 000 r/min离心制备血清。用ELISA法测定血清中VDBP含量,用全自动生化分析仪测定血清中的丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)、总胆红素(total bilirubin,TBIL)、总胆汁酸(total biliary acid,TBA)、胆碱酯酶(cholinesterase,CHE)、谷氨酸脱氢酶(glutamate dehydrogenase,GLDH)、5'核苷酸酶(5'-nucleoticlase,5'-NT)、单胺氧化酶(monoamine oxidase,MAO)和苹果酸脱氢酶(malate dehydrogenase,MDH)含量。实验组与对照组进行t检验分析,检查指标值的差异是否具有统计学意义。结果 在CCl4肝毒性模型中,与对照组相比,ALT,AST,TBIL和CHE在CCl4给药后4 h起升高,差异均具有统计学意义(均P<0.05)。GLDH,MAO和MDH在给药后6 h起升高,差异均具有统计学意义(均P<0.05)。在KTZ肝毒性模型中,与对照组相比,ALT在KTZ给药6天后升高,差异具有统计学意义(P<0.05)。AST和TBIL在给药后8天升高,差异具有统计学意义(P<0.05)。在APAP肝毒性模型中,与对照组相比,ALP在APAP给药后4 h和8 h点升高,差异具有统计学意义(P<0.05)。CHE在给药后8 h点升高,差异具有统计学意义(P<0.05)。ALT和TBIL在给药后24 h点升高,差异具有统计学意义(P<0.05)。在3种肝毒性模型中,VDBP含量在给药后的所有时间点都降低,差异均具有统计学意义(均P<0.05)。结论 VDBP比其它肝功能指标能更灵敏地预测肝毒性的发生。
Abstract:
Objective To evaluate the value of serum vitamin D binding protein(VDBP)in the diagnosis of hepatotoxicity in rats.Methods Three hepatotoxicity models were constructed in male ratswith ketoconazole(KTZ),carbon tetrachloride(CCl4)and acetaminophen(APAP),peripheral blood was collected from large abdominal veins at different time points and serum was prepared by 3 000 r/min centrifugation.The concentration of VDBP in serum was determined by ELISA,and the contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bilirubin(TBIL),total biliary acid(TBA),cholinesterase(CHE),glutamate dehydrogenase(GLDH),5'-nucleoticlase(5'-NT),monoamine oxidase(MAO)and malate dehydrogenase(MDH)in serum were determined by automatic biochemical analyzer.The t test was carried out in the experimental group and the control group tocheck whether the differences in the indicators of each time point were statistically significant.Results In the CCl4 hepatotoxicitymodel,compared with control group,ALT,AST,TBIL and CHE increased from 4h after CCl4 administration,and the difference was statistically significant(P<0.05).GLDH,MAO and MDH increased from 6h,and the difference was statistically significant(P<0.05).In the KTZ hepatotoxicity model,compared with control group,ALT increased from 6 days after KTZ administration,and the difference was statistically significant(P<0.05).AST and TBIL increased at 8 days,and the difference was statistically significant(P<0.05).In the APAPhepatotoxicity model,compared with control group,ALP increased at 4h and 8h after APAP administration,and the difference was statistically significant(P<0.05).CHE increased at 8h,and the difference was statistically significant(P<0.05).ALT and TBIL increased at 24 h,and the difference was statistically significant(P<0.05).VDBP concentration dropped at all time points after administration in three hepatotoxicity models,and the difference was statistically significant(P<0.05).Conclusion VDBP is more sensitive than other liver function indicators to predict the occurrence ofhepatotoxicity.

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备注/Memo

备注/Memo:
基金项目:国家“重大新药创制”科技重大专项(2018ZX09201017)。 作者简介:苗玉发(1980-),男,硕士,副主任药师,主要研究方向为药物安全性评价,E-mail:miaoyufa@nifdc.org.cn。 通讯作者:张河战,研究员,E-mail:zhanghz@nifdc.org.cn。收稿日期:2019-05-14 修回日期:2019-05-17
更新日期/Last Update: 2019-07-30