CAJ | 학술논문

目的：探讨4种 miRNAs （ miRNA －122、miRNA －192、miRNA －193及miRNA－125b1）在异烟肼致大鼠肝损伤的表达水平变化。方法 SD大鼠随机分为实验组48只和对照组8只。实验组给予异烟肼55 mg? kg－1? d－1，连续灌胃3，7，10，14，21，28 d，对照组给予等容积蒸馏水。肝组织经苏木精－伊红（HE）染色观察病理改变；测定血清谷丙转氨酶（ALT）、谷草转氨酶（AST）活性；实时荧光定量聚合酶链式反应（ PCR ）检测肝组织4种 miRNAs 表达水平。结果随着给药时间延长，miRNA－122、miRNA－192及miRNA－125b1表达水平整体下调（均P＜0．01），均在3 d明显下降（均P＜0．01）；miRNA－193表达水平整体上调（P＜0．01），10 d上调明显（P＜0．05）。肝组织病理变化7 d出现肝损伤。血浆 ALT、AST 水平整体上调（均 P ＜0．01），均在10 d 上调明显（P＜0．05）。miRNA－122、miRNA－192、miRNA－125b1发生低表达时间均早于ALT、AST及病理变化，均与 ALT、AST 存在线性相关（均 P ＜0．05），且4种miRNAs表达之间也存在线性相关（均 P ＜0．05）。结论 miRNA －122、miRNA－192及miRNA－125b1发生异常低表达的时间均早于ALT、AST，可能是异烟肼致肝损伤的早期预警指标。
목적：탐토4충 miRNAs （ miRNA －122、miRNA －192、miRNA －193급miRNA－125b1）재이연정치대서간손상적표체수평변화。방법 SD대서수궤분위실험조48지화대조조8지。실험조급여이연정55 mg? kg－1? d－1，련속관위3，7，10，14，21，28 d，대조조급여등용적증류수。간조직경소목정－이홍（HE）염색관찰병리개변；측정혈청곡병전안매（ALT）、곡초전안매（AST）활성；실시형광정량취합매련식반응（ PCR ）검측간조직4충 miRNAs 표체수평。결과수착급약시간연장，miRNA－122、miRNA－192급miRNA－125b1표체수평정체하조（균P＜0．01），균재3 d명현하강（균P＜0．01）；miRNA－193표체수평정체상조（P＜0．01），10 d상조명현（P＜0．05）。간조직병리변화7 d출현간손상。혈장 ALT、AST 수평정체상조（균 P ＜0．01），균재10 d 상조명현（P＜0．05）。miRNA－122、miRNA－192、miRNA－125b1발생저표체시간균조우ALT、AST급병리변화，균여 ALT、AST 존재선성상관（균 P ＜0．05），차4충miRNAs표체지간야존재선성상관（균 P ＜0．05）。결론 miRNA －122、miRNA－192급miRNA－125b1발생이상저표체적시간균조우ALT、AST，가능시이연정치간손상적조기예경지표。
Objective To explore the changes of expression level of four miRNAs ( miRNA -122, miRNA -192, miRNA -193, miRNA -125 b1 ) in isoniazid-induced liver injury rats.Methods The rats were randomly divided into six experimental groups and control group.The experimental groups were given isoniazid orally at 55 mg? kg-1? d-1 for 3 , 7 , 10 , 14 , 21 and 28 days and control group was given saline.The pathological changes of liver were observed by light microscope with HE staining.The activity of serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) were measured. The expression of miRNAs were determined by real -time fluorescent quantitative PCR. Results With medication time extension, the expression of miRNA-122, miRNA-192 and miRNA-125b1 declined (P<0.01) and significantly lower in 3 days ( P <0.01 ) .While miRNA -193 increased and had a sharp increase at 10 days ( P <0.01 ) . The pathology of liver tissues indicated that liver injury happened at 7 days. The serum activity of ALT, AST showed a trend of increase and had a sharp increase at 10 days ( P <0.01 ) . The abnormal expression of miRNA-122 , miRNA -192 and miRNA -125 b1 were earlier than ALT, AST and pathological changes and had linear correlation with ALT and AST ( P<0.05).In addition, there were linear correlation between four miRNAs ( P <0.05 ) . Conclusion The abnormal expression of miRNA -122 , miRNA-192 and miRNA-125b1 were earlier than ALT and AST, which might be severed as a novel candidate bio-markers for isoniazid-induced liver injury.