CCl4致大鼠肝损伤24 h生物标志物水平的变化规律

Changes of CCl4-induced of Liver Injury in Rats for 24 Hours

目的:采用四氯化碳(CCl4)复制大鼠肝损伤的动物模型,研究肝损伤早期生物标志物谷氨酸脱氢酶(GLDH),嘌呤核苷酸磷酸化酶(PNP),α-谷胱甘肽-S-转移酶(α-GST),精氨酸酶1(Arg1)的动态变化,为急性肝损伤的早期发现提供实验依据。方法:48只Wistar大鼠,随机分为正常组和模型组,模型组腹腔注射10%的CCl4橄榄油溶液10 m L·kg^-1,禁食不禁水,于3,6,12,24 h后处死各组动物,测定血清肝功能丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),胆红素(TBIL),碱性磷酸酶(ALP)的水平,α-GST,Arg1,GLDH,PNP水平,肝匀浆超氧化物歧化酶(SOD),谷胱甘肽(GSH),丙二醛(MDA)的水平。结果:与正常组比较,给药3 h后ALT,AST,TBIL,α-GST,Arg1,GLDH,PNP,MDA水平显著升高,SOD明显下降(P <0. 01),给药6,12 h后ALT,AST,α-GST,Arg1,GLDH,TBIL,ALP,MDA水平显著升高,GSH,SOD明显下降(P <0. 05,P <0. 01),给药24 h后ALT,AST,α-GST,Arg1,TBIL,ALP,MDA水平显著升高,GSH,SOD显著下降(P <0. 01)。结论:α-GST,Arg1,GLDH,PNP较传统肝功能检测指标具有较好的灵敏性,可用于CCl4致大鼠肝损伤早期检测。

Objective: To replicate the animal model of liver injury in rats by using carbon tetrachloride( CCl4),investigate the dynamic changes of early biomarkers of liver injury,namely glutamate dehydrogenase( GLDH),purine nucleotide phosphorylase( PNP),α-dynamic changes of glutathione-S-transferase( α-GST) and arginase 1( Arg1),and provide experimental evidence for early detection of acute liver injury. Method: Fortyeight Wistar rats were randomly divided into a blank group and a model group. The model group was intraperitoneally injected with 10 m L·kg^-10% CCl4 olive oil solution,fasting but except water. Animals were sacrificed at 3,6,12, and 24 h. The serum liver function alanine aminotransferase( ALT), aspartate aminotransferase( AST),bilirubin( TBIL),alkaline phosphatase( ALP) levels,α-GST,Arg1,GLDH,PNP levels,and liver homogenate superoxide dismutase( SOD),glutathione( GSH),malondialdehyde( MDA) levels were then detected. Result: As compared with blank group,the levels of ALT,AST,TBIL,α-GST,Arg1,GLDH,PNP and MDA were increased significantly 3 h after administration,and SOD was decreased significantly( P < 0. 01). After 6,12 h,the levels of ALT,AST,α-GST,ARG-,GLDH,TBIL,ALP and MDA were increased significantly,while GSH and SOD were decreased significantly( P < 0. 05,P < 0. 01). After 24 h,the levels of ALT,AST,α-GST,Arg1,TBIL,ALP and MDA were significantly increased,while GSH and SOD were significantly decreased( P < 0. 01). Conclusion: α-GST,Arg1,GLDH and PNP have better sensitivity than traditional liver function test indicators,and can be used for early detection of liver injury induced by CCl4 in rats.