体内转染RXR-α基因对大鼠肝纤维化的影响

Impact of in vivo Transfection of RXR-α Gene on Liver Fibrosis in Rats

肝纤维化常伴维甲类X受体α（RXR-α）表达下降.目的：探讨增加肝脏RXR-α表达对大鼠肝纤维化的抑制作用.方法：以CCl4诱导大鼠肝纤维化模型,尾静脉注射RXR-α基因重组慢病毒载体.实验设肝纤维化模型组、空白载体转染组、RXR-α转染组和正常对照组,均包括2周和8周两个时间点.组织病理学检查肝纤维化程度,测定肝组织羟脯氨酸（Hyp）含量,蛋白质印迹法检测肝组织RXR-α、α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原表达情况.结果：肝组织病理学检查显示正常对照组的肝纤维化分期均为So,模型组和空白载体转染组为S2（2周）和S3（8周）,RXR-α转染组为S1（2周）和S2（8周）.模型组肝组织Hyp、α-SMA和Ⅰ型胶原含量高于正常对照组,RXR-α含量低于正常对照组,差异均有统计学意义（P〈0.01）;模型组与空白载体转染组间差异无统计学意义（P〉0.05）;RXR-α转染组Hyp、α-SMA和Ⅰ型胶原含量低于模型组和空白载体转染组,RXR-α含量高于模型组和空白载体转染组,差异均有统计学意义（P〈0.01）.结论：对于早期肝纤维化,提高肝内RXR-α表达可部分抑制纤维化并逆转部分纤维化相关指标：对于已发生的肝纤维化,则仅能部分抑制肝纤维化而无法使相关指标恢复正常.

Background： Expression of retinoic X receptor-α （RXR-α） was decreased in liver fibrosis. Aims： To study whether increased expression of RXR-α can inhibit liver fibrosis in rats. Methods： Liver fibrosis was induced by CC14 in rats, and recombinant lentivirus vector of RXR-α was injected through the tail vein. Rats were randomized into fibrosis group, sham-transfected group, RXR-α transfected group and normal control group, each group further divided into 2-week and 8-week subgroups. Liver fibrosis was examined by histological examination, and liver hydroxyproline （Hyp） content was determined. Protein levels of liver RXR-α, α-smooth muscle actin （α-SMA） and type I collagen were detected by Western blotting. Results： The stages of liver fibrosis in normal control group, fibrosis group, sham-transfected group, and RXR-α transfected group were SO, S2 （2-week） and S3 （8-week）, S2 （2-week） and S3 （8-week）, S1 （2-week） and S2 （8- week）, respectively. Liver Hyp content and levels of cc-SMA, type I collagen in fibrosis group were higher than those in normal control group （P〈0.01）, while level of RXR-α was lower than that in normal control group （P〈0.01）. There was no difference between fibrosis group and sham-transfected group （P〉0.05）. Liver Hyp content and levels of α-SMA, type I collagen in RXR-α transfected group were lower than those in fibrosis group and sham-transfected group （P〈0.01）, while level of RXR-α was higher than that in fibrosis group and sham-transfected group （P〈0.01）. Conclusions： For those with early liver fibrosis, increasing the expression of RXR-α can inhibit liver fibrosis to some extent and reverse some of the relevant indexes to normal range. While for those with liver fibrosis, increasing the expression of RXR-α can only inhibit liver fibrosis to some extent, but cannot reverse the relevant indexes to normal range.