目的 观察重组腺相关病毒rAAV/NT4-AcSDKP对四氯化碳(CCl4)诱导的小鼠肝纤维化的影响.方法 30只昆明雌性小鼠随机分为正常对照组、模型组和干预组,造模采用200 mL/L CCl4花生油混合液腹腔注射致小鼠肝纤维化模型,共8周,干预组小鼠在加害4周后注射重组腺相关病毒.于8周实验结束时处理存活的全部小鼠,观察重组病毒对小鼠肝组织病理变化、肝功能生化指标以及肝纤维化指标等的影响,以及NT4-AcSDKP在肝组织中的表达变化.结果 融合基因在干预组肝组织中表达并且重组腺相关病毒对CCl4引起的肝组织病理有明显改善；与模型组相比,干预组小鼠的肝纤维化指标透明质酸(HA)、层黏蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)的P值分别为0.00、0.00、0.01、0.03,P＜0.05,差异具有统计学意义；但是谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBIL)、总蛋白(TP)、白蛋白(Alb)等肝功能生化指标的P值分别为o.89、0.38、0.58、0.32、0.32,均为P＞0.05,差异无统计学意义.结论 携带NT4-AcSDKP融合基因的重组腺相关病毒对CCl4引起的小鼠肝纤维化有一定的保护作用,与近期用商品化四肽保护CCl4诱导的小鼠肝纤维化作用保持一致.%Objective To observe the effect of the rAAV-NT4-AcSDKP on carbon tetrachloride (CC1, )-induced liver fibrosis in mice. Methods A total of 30 Kunming female mice were divided into normal control group, model group and intervention group. The model of liver fibrosis in mice was induced by intraperitoneal injection of 200 mL/L mixed oil-CCl4 solution for 8 weeks. The rAAV was injected into mice of intervention group at week 4 and then the changes of histological appearance, liver function parameters and fibrosis parameters were observed at the end of the experiment. RT-PCR was used to detect the expression of NT4-AcSDKP in the mice livers. Results The fusion gene NT4-AcSDKP was expressed in the intervention group and protected the mice in histological appearance. P of fibrosis parameters, namely, HA, LN, PCⅢ and CⅣ was 0.00, 0.00, 0.01 and 0.03, respectively, which differed significantly from that in the model group (P<0.05). However, P of liver function parameters AST, ALT, TBIL, TP or Alb was 0. 89, 0.38, 0.58, 0.32 and 0.32, which had no significant difference (P>0.05). Conclusion The recombinant adeno-associated virus rAAV-NT4-AcSDKP plays a certain role in protecting mice from CC14-induced liver fibrosis, which is consistent with the antifibrotic effect of AcSDKP protein in the finished product.
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