Hyper-IL-6重组慢病毒对大鼠急性肝衰竭的保护作用

Protective effect of recombinant lentivirus-mediated hyper-interleukin-6 on rats with acute liver failure

目的:探讨重组慢病毒介导的超级白细胞介素6(Hyper-IL-6)对大鼠急性肝衰竭的保护作用及机制。方法:45只D-氨基半乳糖急性肝衰竭模型大鼠随机分为3组:FIV-HIL-6组、FIV-IL-6组及未感染组,造模前2小时分别给予腹腔注射FIV-HIL-6、FIV-IL-6和生理盐水,造模后12、24、48、72小时及7天时进行肝功能、内毒素、肝组织脂质过氧化水平(MDA、SOD)及光镜、电镜检查,并用逆转录PCR检测7天时肝组织目的基因整合状况。另取16只正常大鼠随机分为2组,分别给予FIV-HIL-6、FIV(空载体)一次性腹腔注射,观察重组慢病毒对大鼠的毒副作用。结果:FIV-HIL-6组血清谷丙/草转氨酶(ALT/AST)、总胆红素(TB)、内毒素、MDA值低于FIV-IL-6组、未感染组,SOD值较高(P<0.05),肝组织病变较轻;重组慢病毒对大鼠无明显毒副作用,大鼠肝脏组织中有目的基因Hyper-IL-6表达。结论:FIV-HIL-6成功转染大鼠肝脏组织,Hyper-IL-6对急性肝衰竭大鼠肝组织有明显的抗炎抗氧化作用,能有效改善大鼠肝功能及肝组织学状况,对急性肝衰竭大鼠具有保护和治疗作用。

Objective：To investigate the protective effect of recombinant lentivirus-mediated hyper-interleukin-6 （Hyper-IL-6） from acute liver failure in rats and its mechanism.Methods：Acute liver failure was triggered by use of D-galactosamine in totally 45 rats,then the rats were randomly divided into 3 groups：FIV（Feline immunodeficiency virus）-Hyper-IL-6 group,FIV-IL-6 group and the control groups （n=15 each）.The rats of each group were intraperitoneally injected with FIV-HIL-6,FIV-IL-6 and normal saline,respectively,at 2 h before modeling.At 12 h,24 h,48 h,72 h and 7 d after modeling,the liver function,endotoxin （ETM）,lipid peroxidation levels （SOD,MDA） in liver tissue were determined.The light microscopy and electron microscopy were applied to observe histomorphological changes.The gene integration in liver tissue was detected by RT-PCR on the 7th day.Another 16 SD rats were randomly divided into 2 groups,which were given FIV-HIL-6,FIV peritoneal injection once,to observe the toxicity of recombinant lentivirus on rats.Results：In FIV-HIL-6 group,serum levels of alanine/grass transaminase （ALT/AST）,total bilirubin （TB） value,MDA and ETM were lower than those in FIV-IL-6 group and non-infected group （P〈0.05）,while SOD value was higher.The recombinant lentivirus was showed no significant toxic effects on rats.Hyper-IL-6 was expressed in liver tissue of the rats.Conclusion：FIV-HIL-6 is successfully transfected in liver tissue of the rats.For the rats with acute liver failure,Hyper-IL-6 has strong anti-inflammatory and antioxidant effects,and effectively improves liver function and histological condition.Hyper-IL-6 has protective and therapeutical effect in rats with a cute liver failure.