转化生长因子α和β1在极限门静脉结扎肝脏组织中的表达及其意义

Study on Significance and Expression of Transforming Growth Factor-α and-β1 after 90% Portal Vein Ligation in Rats

目的探讨转化生长因子(TGF)-α和TGF-β1在90%极限门静脉分支结扎大鼠肝脏组织中的表达及其与肝脏再生的关系。方法 SD雄性大鼠96只,随机平均分成假手术组和门静脉结扎(PBL)组,观察术后0.5、1、3、5、7、14、21和28d总肝脏和未结扎侧肝脏质量变化,光学显微镜下观察未结扎侧肝细胞的形态变化,用免疫组化方法检测未结扎侧肝细胞的增殖细胞核抗原(PCNA)及TGF-α和TGF-β1的表达。结果 90%极限门静脉分支结扎后,结扎侧肝叶呈进行性萎缩、变小,未结扎侧肝叶占总肝质量的比例在术后1d内增加较缓慢,而在术后1～5d增加速度明显加快,5d以后增加变慢,于7d达"平台期"。与假手术组比较,PBL组术后肝组织中PCNA表达在术后0.5～3d明显增多(P<0.01),术后5d达高峰,7d有所减少,但仍高于假手术组(P<0.01),以后减少接近假手术组。假手术组术后肝脏可见少量TGF-α和TGF-β1表达,PBL组大鼠未结扎侧肝叶术后0.5d开始两者表达量增加,分别至术后3d和1d达高峰(P<0.05),术后7～28d下降并接近假手术组(P>0.05)。结论大鼠90%PBL术后导致未结扎侧肝脏再生,而TGF-α和TGF-β1蛋白表达与肝脏再生启动和增殖过程密切相关。

Objective To investigate the expressions of transforming growth factor （TGF）-α and-β1 after 90% portal branch ligation （PBL） in rats.Methods Ninety-six SD rats were randomly divided into sham operation group and portal vein branches ligation group.The weight of both ligated and unligated lobes of liver were measured on 0.5,1,3,5,7,14,21,and 28 d after operation.The morphological changes of the unligated liver lobes were observed by microscope.The expressions of proliferating cell nuclear antigen （PCNA）,TGF-α,and TGF-β1 of the unligated liver lobes were detected by immunohistochemistry.Results After the ligation of 90% portal vein branches,hepatic lobe at the ligated side diminished progressively after ligation,whereas the lobes of the unligated side underwent compensatory regeneration.The ratio of unligated lobes weight to the whole liver increased slowly within 1 d,speeded up significantly during 1-5 d period,increased slowly on 5 d,and reached plateau phase on 7 d after operation.The expressions of PCNA protein markedly increased within 0.5-3 d （P〈0.01）,which reached the peak on 5 d and decreased slightly on 7 d after operation,but still higher than sham operation group level,and then gradually returned to the level of sham operation group lately.The expressions of TGF-α and TGF-β1 in the unligated liver lobes markedly increased on 0.5 d,and reached the peak on 3 d and 1 d respectively,and then gradually returned to the level of sham operation group in 7-28 d after operation.Conclusion Ligation of 90% portal branches can induce active regeneration of unligated liver lobes in rats,whose initiation and proliferation are involved in the expressions of TGF-α and TGF-β1 protein.