恩替卡韦对急性重型乙肝模型小鼠肝脏趋化因子IP-10 mRNA和血清TGF-β1的影响

Effects of entecavir on hepatic chemokine IP-10 mRNA and serum TGF-β1 in acute severe hepatitis B mice

[目的]探讨恩替卡韦影响急性重型乙肝模型小鼠肝脏趋化因子γ干扰素诱导蛋白-10(IP-10)mRNA和血清转化生长因子-β1(TGF-β1)表达的机制。[方法]将54只BABL/cJ小鼠随机均分为对照组、模型组和恩替卡韦组。造模时将100μl滴度1×10~6 PFU/ml的Ⅲ型鼠肝炎病毒(MHV-3)质粒经尾静脉注射造成乙型肝炎病毒(HBV)急性感染;造模完成后,恩替卡韦组用10%恩替卡韦0.5ml/(10g·d)灌胃治疗21d,模型组及对照组用生理盐水按0.5ml/(10g·d)灌胃治疗21d。在造模后和治疗21d后采用PCR法对小鼠肝脏IP-10 mRNA和眶静脉血血清HBV-DNA进行定量分析,并检测血清TGF-β1、白细胞介素-10(IL-10)、Ⅳ型胶原蛋白(cⅣ)、Ⅲ型胶原蛋白(PC-Ⅲ)、层黏连蛋白(LN)、透明质酸(HA)和肝功能。[结果]治疗21d后,与模型组比较,恩替卡韦组小鼠肝脏IP-10 mRNA呈低表达,血清HBV-DNA滴度显著降低(P<0.05);血清纤维化指标中TGF-β1、LN和HA水平明显降低(P<0.05);肝功能中AST、TBIL、GGT、ALT和TBA水平均明显降低(P<0.05)。[结论]恩替卡韦可渗入到HBV-DNA链中,阻断DNA合成,抑制IP-10 mRNA的表达,减少IL-10对肝细胞的炎性损伤,阻止肝组织纤维化病变从而促进肝功能的恢复。

[Objective]To investigate the mechanism of entecavir influencing on the expression of liver chemokine gamma interferon inducible protein-10（IP-10）mRNA and serum transforming growth factor-β1（TGF-β1）in mice with acute severe hepatitis B.[Methods]Fifty-four BABL/cJ mice were randomly divided into control group,model group and entecavir group.For modeling,100μl plasmid of MHV-3 strain at a titer of 1×10~6 PFU/ml was injected via the tail vein to induce acute hepatitis B virus（HBV）infection.After modeling,the entecavir group was intragastrically treated with 10% entecavir 0.5 ml/（10 g·d）for 21 days,while,the model group and the control group were treated with 10% saline 0.5 ml/（10 g·d）for 21 days.After modeling and 21 days of treatment,the IP-10 mRNA in liver and orbital blood serum HBVDNA of mice were quantitatively analyzed by PCR,and the levels of TGF-β1,interleukin-10（IL-10）,typeⅣcollagen（cⅣ）,typeⅢ collagen（PC-Ⅲ）,laminin（LN）,hyaluronic acid（HA）and liver function were tested.[Results]After 21 days of treatment,the expression of IP-10 mRNA in liver,the serum HBV-DNA titer,the serum fibrosis indicators of TGF-β1,LN and HA,the levels of AST,TBIL,GGT,ALT and TBA in entecavir group were significantly lower than that in model group（P〈0.05）.[Conclusion]Entecavir can penetrate into the HBV-DNA chain,blocking DNA synthesis,inhibiting the expression of IP-10 mRNA,reduc-ing the inflammatory injury of liver cell by IL-10,preventing the fibrosis of liver tissue and promoting the recovery of liver function.