Bax、Bcl-2和NF-κB在肝再生早期中的表达

The expression of Bax, Bcl-2 and NF-κB in the early stage of liver regeneration

目的研究在大鼠大部肝切除(partial hepatectomy,PH)术后细胞凋亡调节基因(Bcl-2 associated X protein Bax)、Bcl-2(B-cell lymphoma-2)及NF-κB(nuclear factor-kappa B)三者的分布和表达,探讨三者在肝再生早期中的调节机制及其相互调控作用。方法采用SD大鼠35只分7组,每组5只构建大鼠肝脏再生模型,并在显微镜下观察肝大部切除后早期(0.5、1、4、6、8、12、24 h)肝组织的形态学变化,采用免疫组织化学SABC法检测Bax、Bcl-2、NF-κB在正常肝组织中的表达,并研究在肝再生早期中的分布及表达变化。结果 Bax、Bcl-2、NF-κB在正常肝组织未见表达,但在PH后30 min,Bax、Bcl-2及NF-κB即在肝细胞和胆管上皮细胞和肝血窦内皮内开始出现表达,PH后6 h表达达到高峰,之后其表达逐渐下降,而Bcl-2的表达一直保持在较高水平。NF-κB于PH后6 h表达出现高峰后其表达逐渐下调,24 h时NF-κB表达上调,出现另一表达高峰。结论肝大部切除后再生早期,存在着凋亡和抑制凋亡的分子调控机制,NF-κB的表达可能与激活Bcl-2、抑制肝细胞的凋亡从而促进肝细胞再生有关。

Objective To research the expression and distribution of Bax, Bcl-2 and NF-κB and discussion their regulating mechanism and the mutual control function in the early stage of liver regeneration after partial hepatectomy. Methods Thirty-five SD rats were used to establish mice model of liver partial hepatectomy according to Higgins 's method. To observe the morphological changes of liver at the early stage(0.5 h,1 h,4 h,6 h,8 h,12 h, 24 h) after the partial hepatectomy. We used Immuno-histochemistry assays to detect the expressing changes of Bax, Bcl-2 and NF-κB in the normal liver and in the early liver regeneration.Results 1 To observe the morphological changes of rat's liver tissues in the early stage of liver regeneration: The liver cells become hyperemia and edema, The gap of hepatic sinusoid increased, it can be observed that the gap of hepatic sinusoid increasd wider after 12 h, the structure of hepatic lobule appeared atypical hyperplasia, it can be observed the binuclear hepatocyte increased, thecavitation phenomenon of liver cells and the infiltration of inflammatory cells. 2It can not be observed the expression of Bax, Bcl-2 and NF-κB in normal liver tissue, but it began to express in liver cells, bile duct epithelial cells and hepatic blood sinus endothelial cells at 30 min, and reached their peak at 6 h after partial hepatectomy, then the expression gradually decreased,but the expression of Bcl-2 remained at a higher level. The expression of NF-κB reached it's peak at 6h then gradually decreased,while at 24 h the expression of NF-κB increased and reached the other peak. Conclusion There are molecular regulation mechanisms of apoptosis and apoptosis resistance in the early stage of liver regeneration, The expression of NF-κB may be relevant to the activation of Bcl-2, the inhibition of the hepatocyte apoptosis so that to promote the regeneration of liver cells.