蚓激酶在慢性乙型肝炎治疗中的潜在作用

Lumbrokinase in a Potential Function to Intervene Chronic Hepatitis B

纤连蛋白(FN)是参与乙型肝炎病毒感染和肝脏纤维化的重要分子.蚓激酶(LK)是从赤子爱胜蚓(Eisenia foetide)中提取的一组蛋白水解同工酶,能水解纤维蛋白治疗凝血相关疾病.从这组同工酶中分离纯化出单一活性成分,在体外可降解纤连蛋白,被命名为蚯蚓纤连蛋白水解酶(EFNase).然而,LK能否预防乙型肝炎病毒感染以及缓解因乙型肝炎导致的肝脏损伤等问题还不清楚.本研究以人肝癌细胞系Hep G2.2.15为细胞模型,观察LK对乙型肝炎表面抗原(HBsAg)或FN水平的影响;以C57BL/6J-HBV转基因小鼠为动物模型,探讨LK对小鼠血清中HBsAg、FN、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平及肝脏病理改变的影响.结果表明,LK在体内外均能抑制HBsAg的生成,降低血清和肝脏FN.与生理盐水处理组相比,LK改善了肝脏的状态.这些数据为理解LK作为治疗乙型肝炎的潜在有效药物的治疗作用提供了有价值的信息.

Fibronectin(FN)is an important molecule that participates in hepatitis B infection and fibrosis.Lumbrokinase(LK)is synthesized by earthworms containing a group of proteolytic isozymes,which were used to hydrolyze fibrin in the treatment of clotting disease.One of the isozymes purified from the LK compound was verified as a hydrolase to degrade FN in vitro and was called earthworm fibronectin hydrolase(EFNase).However,whether LK functions to prevent the deterioration of hepatitis B virus(HBV)infection has not been clarified.In this study,we used HepG2.2.15 cells to investigate the effect of LK on the level of hepatitis B surface antigen(HBsAg)or FN,used C57BL/6J-HBV transgenic mice to explore the effect on the level of HBsAg,FN,alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum,the pathological changes in livers.The results indicated that LK could inhibit HBsAg production in vitro and in vivo;decreased FN in serum and liver.Compared with physiological saline,LK improved the state of the livers.Those data provided valuable information to understand the therapeutic role of LK as a potentially effective medicine to treat chronic hepatitis B(CHB).