肝活素（HPS）--一种新的小鼠急性肝损伤标志物

摘要

目的：急性肝衰竭是目前临床上导致死亡的重要病因之一，研究具有肝特异性、灵敏度高的肝损伤标志物对于严重肝病的早期诊断以及预后预测具有重要的意义。肝活素（ hepassocin，HPS）是一种具有高度组织特异性的促肝细胞增殖活性因子，在动物水平检测其在血清中的表达水平与肝损伤程度的相关性将为其开发成临床检测急性肝损伤的特异性标志物奠定基础。方法利用腹腔注射不同剂量CCl4处理诱导小鼠急性肝损伤模型，检测小鼠的存活率、转氨酶水平以及肝病理变化。通过ELISA检测小鼠血清的HPS水平；实时PCR法检测HPS mRNA水平；Western印迹法检测HPS的蛋白表达水平。结果随着CCl4处理剂量的增加，小鼠死亡率显著升高，肝损伤程度显著增加，在此过程中，HPS在小鼠血清及肝组织中的表达水平也显著上调，并与肝损伤程度密切相关。结论HPS可做为一种新的小鼠肝损伤标志物。%Objective Acute liver failure is one of the significant causes of death clinically.It is important to explore new serum markers of liver injury for early diagnosis and prognosis prediction of severe liver disease.Hepassocin ( HPS) is a liver-specific mitogenic growth factor.Our study is intended to investigate the correlation between HPS serum levels and the degree of liver injury.Methods Firstly, a mouse model of acute liver injury was constructed via intraperitoneally injection with different doses of CCl4 .Then the survival rate, alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) and the pathological changes in the liver were detected.Meanwhile, ELISA assay was performed to detect the serum level of HPS.In addition, the mRNA level and protein level of HPS were detected by real-time PCR and Western blotting, respectively.Results The mortality rate was increased and the liver damage was aggravated with the increase of the CCl4 dose.Besides, the ALT and AST levels were also increased in a dose-dependent manner.Additionally, the mRNA and protein levels of HPS were significantly up-regulated and closely related to the degree of the liver injury in the model. Conclusion HPS can be used as a new marker of liver injury in mice.