慢病毒介导PXR体内转染对CCl_4诱导的大鼠肝损伤的保护作用研究  

Protective effects of lentivirus-mediated PXR transfection in vivo on CCl4-induced liver injury in rat

作　　者：张韬 程变巧[3] 林伟国[3] 朱琪[3] 

机构地区：[1]福建省医学科学研究院免疫研究所,福州350001 [2]福建省医学测试重点实验室,福州350001 [3]厦门大学附属福州第二医院肝胆内科,福州3500071

出　　处：《中国肝脏病杂志（电子版）》2015年第1期10-14,共5页Chinese Journal of Liver Diseases：Electronic Version

基　　金：2013年福建省自然科学基金面上项目(2013J01282)

摘　　要：目的探讨PXR对CCl4诱导的大鼠肝损伤的保护作用。方法雄性SD大鼠48只,随机分为4组,空白组不做任何处理;模型组通过CCl4灌胃诱导肝损伤;空载体组在建立肝损伤模型前3天静脉注射慢病毒空载体;PXR慢病毒组在建立肝损伤模型前3天静脉注射PXR重组慢病毒。通过血清AST和ALT检测和肝脏HE染色评估肝损伤程度;Western blot及RT-PCR检测大鼠肝组织中PXR、NF-κB、IL-1、IL-2和TNF-α的表达。结果慢病毒介导PXR体内转染后肝损伤大鼠血清AST和ALT明显降低,肝损伤及纤维化程度明显减轻,PXR表达水平明显升高,相反,NF-κB、IL-1、IL-2和TNF-α的表达水平明显降低。结论 PXR可能通过抑制NF-κB的表达,下调炎症相关因子IL-1、IL-2和TNF-α的表达,从而对CCl4诱导的大鼠肝损伤具有一定的保护作用,可为肝损伤的治疗提供一种新的途径和思路。Objective To investigate the protective effect of PXR in CCl4-induced liver injury in rat. Methods Forty eight Sprague-Dawley male rats were randomly divided into four groups： control group（without treatment）; model group, which was treated with CCl4 to induce liver injury; empty vector group, which was intravenously injected with lentiviral vector three days before liver injury; PXR recombinant lentivirus group was intravenously injected with PXR recombinant lentivirus three days before liver injury. The degree of liver injury was evaluated by HE staining and levels of serum AST and ALT. The expression of PXR, NF-κB, IL-1, IL-2 and TNF-α in liver were assayed by RT-PCR and Western blot. Results After intravenous injection with PXR recombinant lentivirus, fibrosis and serum AST and ALT in rat with liver injury reduced significantly. The expression of PXR in liver increased significantly. On the contrary, the expression of NF-κB, IL-1, IL-2 and TNF-α in liver decreased significantly. Conclusions PXR plays a protective role in CCl4-induced liver injury in rat. It may through inhibit the expression of NF-κB, further to down-regulate the expression of IL-1, IL-2 and TNF-α, which provides a new way for treatment of liver injury.

关 键 词：慢病毒属 大鼠 转染 

分 类 号：R575[医药卫生—消化系统]