血清微小RNA在中药肝毒性临床前评价中的应用研究

Study on the application of serum microRNA in preclinical evaluation for hepatotoxicity induced by herbal medicines

通过对19种具有潜在肝脏毒性的中草药进行临床前安全性评价,在观测体重、摄食量、血清生化指标、脏器系数与肝脏组织病理学改变的同时,探讨血清微小RNA(miRNA)作为新型候选标志物在中草药肝损伤诊断中的应用价值。结果表明:与溶剂对照组相比,血清miRNA-122水平显著升高的给药组有6组,而血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平显著升高的分别为2组和3组,其中五倍子组表现为急性药源性肝损伤。在血清miRNA-122的时间相关性和剂量相关性分析中,与血清ALT和AST相比,血清miRNA-122呈现出更高的敏感性,表现为更早期和更大幅度的显著升高。说明血清miRNA-122可作为中草药肝损伤的新型候选诊断标志物,与肝脏组织病理学改变具有良好的相关性,且较传统血清生化学指标更为敏感。

The diagnostic value of serum miRNA-122,which severs as a novel candidate biomarker for herb-induced liver injury,was studied through a preclinical safety evaluation on 19 potential hepatotoxic herbal medicines.In the meanwhile,parameters including body weight,food intake,blood chemistry indicators,organ-to-body-weight ratio and histopathological changes were also observed in this evaluation.The results showed that,by comparison with the vehicle group,serum miRNA-122 significantly elevated in 6 treatment groups,while serum ALT and AST significantly elevated in 2 and 3 treatment groups,respectively.Among the herbs tested,Calla Chinensis could induce acute liver injuries.In time-and dose-related analysis,serum miRNA-122 displayed better sensitivity with the characteristics of earlier appearance and larger fold change than serum ALT and AST.This study demonstrates that serum miRNA-122,which severs as a novel candidate biomarker for herb-induced liver injury,is correlated well with the results of histomorphologic examinations and is much more sensitive than conventional blood chemistry indicators.