胆道外引流对大鼠肝再生的影响及其细胞周期调控机制

目的: 观察胆道外引流(ED)对大鼠肝再生及肝细胞周期的影响。方法: 采用大鼠70％肝切除模型,SD大鼠随机分成6组,每组8只,分别为正常切肝24 h组、48 h组,阻塞性黄疸(OJ)切肝24 h组、48 h组,OJ后ED 3 d切肝24 h组、48 h组。采用增殖细胞核抗原(PCNA)标记和Feulgen染色测定肝再生能力;采用RT-PCR 测定肝组织肝细胞生长因子(HGF)、p27和cyclin D1 mRNA水平变化;免疫组化法测定HGF、转化生长因子β₁(TGF-β₁)和p21在肝细胞的表达。结果: OJ切肝后PCNA标记指数较对照组低(P<0.05),ED后PCNA标记指数更低,与OJ组对比差异显著(P<0.05)。DNA含量变化与PCNA标记指数相似。与正常切肝组比较,OJ后切肝组HGF mRNA下降(P<0.05),ED后切肝组进一步下降并较OJ组低(P<0.05)。与正常组相比,OJ后切肝24 h和48 h cyclin D1 mRNA均下降(P<0.05,P<0.01),ED后切肝组进一步下降,但差异不显著。与正常切肝组相比,48 h时OJ后切肝组高于正常切肝组(P<0.05),ED后p27 mRNA水平较OJ进一步升高(P<0.05)。与正常切肝组比较,OJ后切肝组肝细胞HGF表达在24 h下降(P<0.05),ED后切肝组进一步下降并较OJ组低(P<0.05)。p21表达各组间无显著差异。与正常切肝组相比,24 h时OJ后切肝组TGF-β₁表达上调,差异显著(P<0.05),ED后切肝组上调,但差异不显著。结论: OJ可造成大鼠肝再生能力下降,ED后其肝再生能力进一步降低。ED后肝再生能力下降可能和HGF、p27密切相关,与TGF-β₁、p21、cyclin D1无关。

Effect of external biliary drainage on liver regeneration and regulatory mechanism of cell cycle in rats

AIM: To investigate the effect of external biliary drainage on the liver regeneration and the regulatory mechanism of cell cycle in rats.METHODS: The SD rats were used to establish the model of 70% partial hepatectomy(PH).The rats were divided into 6 groups,including normal rats with PH for 24 h or 48 h,obstructive jaundice(OJ) rats with PH for 24 h or 48 h and external drainage(ED) rats with PH for 24 h or 48 h.PCNA labeling index(LI) and DNA content(Feulgen staining,PU value) were measured.The mRNA expres...