二肽基肽酶-4在慢性肝病发病中的作用研究进展

What roles does dipeptidyl peptidase- 4 play in chronic liver diseases?

二肽基肽酶-4(DPP-4)是膜相关酶,又称T细胞表面抗原CD26,在体内广泛分布,作用广泛。最有代表的作用靶肽是胰高血糖素样肽(GLP)-1,而GLP-1的失活导致糖耐量减低和糖尿病。除了其肽酶作用之外,DPP-4与免疫激活密切相关,结合并降解细胞外基质,对抗抗癌剂以及脂质积累。最近的研究表明,肝脏表达高水平的DPP-4,DPP-4在各种慢性肝病(如丙型肝炎病毒感染、非酒精性脂肪性肝病和肝细胞癌)的发病中有一定的作用。此外,在肝脏,干细胞也表达DPP-4,提示其在肝移植中有重要作用。本文介绍了DPP-4的分布及生物活性,重点讨论了DPP-4在慢性肝病发病中的作用以及DPP-4抑制剂的临床应用前景。

Dipeptidyl peptidase-4 （DPP-4） is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and has pleiotropic effects. A representative target peptide is glucagon-like peptide-1 （GLP-1）,and inactivation of GLP-1 results in the development of glucose intolerance/diabetes mellitus. In addition to its peptidase activity,DPP-4 is associated with immune stimulation,binding to and degradation of extracellular matrix,resistance to anti-cancer agents,and lipid accumulation. The liver expresses DPP-4 to a higher degree,and recent studies suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection,non-alcoholic fatty liver disease,and hepatocellular carcinoma. Furthermore,hepatic stem cel s express DPP-4,which might plays a crucial role in hepatic regeneration. In this paper,we reviewed the tissue distribution and various biological effects of DPP-4. The impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor were also discussed.