术前胆道外引流对恶性阻塞性黄疸患者肝再生的影响及其细胞周期调控机制

摘要

Objective To investigate the effect of preoperative biliary drainage (PBD) on heptocyte proliferation and cell cycle regulation mechanism in malignancies with obstructivejaundice.Methods Patients with malignant obstructive jaundice were divided into PBD group (15 cases) and NPBD group (15 cases)randomly.At the same time,10 patients with hepatic hemangiomas were taken as control group.PCNA LI and DNA content (Feulgen stain,PU value) were measured; Cyclin D1,p27mRNA,p21,HGF,TGF-β1 were also detected in hepatic tissue.Results The PCNA LI in 3 groups was significantly different (F =17.39,P＜0.01).The PCNA LI in NPBD group was significantly higher than that in control group (P =0.000),and the PCNA LI in PBD group was higher than that in NPBD group (P =0.013).Consistently,the changes of hepatocyte PU value is similar to the result of PCNA LI.The cyclinD1 mRNA/GAPDH mRNA in 3 groups was significantly different (F=11.19,P ＜0.01).The cyclinD1 mRNA/GAPDH mRNA in NPBD group was significantly higher than in control group (P =0.003),and the cyclinD1 mRNA/GAPDH mRNA in NPBD group was higher than in PBD group (P=0.029).The p27 mRNA/GAPDH mRNA in 3 groups was significantly different (F =7.03,P ＜ 0.05).The p27 mRNA/GAPDH mRNA in NPBD group was significantly lower than in control group (P =0.014),and the p27 mRNA/GAPDH mRNA in PBD group was lower than in NPBD group (P =0.031).The HGF in 3 groups was significantly different (F =17.40,P ＜ 0.05),but was not statistically significant between NPBD and PBD (P =0.371).There was no statistically significant difference in the expression of p21 among groups.Conclusions As an injury factor to liver,malignant obstructive can promote proliferation of hepatocytes and PBD can further enhance this effect.Cyclin D1,p27 and TGF-β1 play certain roles incell cycle regulation mechanism related to this condition.p21 does not seem to be involved in this mechanism.%目的 探讨术前胆道外引流减黄对恶性阻塞性黄疸患者肝再生能力的影响以及其细胞周期调控机制.方法 将恶性阻塞性黄疸手术患者30例随机分为减黄组和未减黄组各15例.另选资料匹配的10例行肝血管瘤手术患者作为对照组.测定各组增殖细胞核抗原(PCNA)标记指数(LI)以及肝细胞DNA含量(Feulgen染色,PU值),并检测肝组织的细胞周期蛋白D1 (Cyclin D1)、p27基因、p21基因、人肝细胞生长因子(HGF)、转化生长因子β1 (TGF-β1).结果 3组PCNA LI均有差异(F=17.39,P＜0.01),减黄组PCNA LI较未减黄组高(P=0.013),未减黄组PCNA LI较对照组高(P=0.000).PU值变化情况与PCNA LI相似.3组肝组织Cyc1in D1 mRNA/GAPDH mRNA差异具有统计学意义(F=11.19,P＜0.01),减黄组较未减黄组高(P=0.029),未减黄组较对照组高(P=0.003).3组肝组织p27 mRNA/GAPDH mRNA比较差异具有统计学意义(F=7.03,P＜0.05),减黄组较未减黄组低(P=0.031),未减黄组较对照组低(P =0.014).3组HGF差异具有统计学意义(F=17.40,P＜0.05),非减黄组肝细胞HGF较对照组高(P =0.000),而非减黄组与减黄组比较差异无统计学意义(P=0.371).p21在各组表达的差异无统计学意义.结论 恶性阻塞性黄疸作为一种肝损伤因子,可以促使肝再生能力增强,而术前减黄后可进一步提高肝再生的能力.Cyclin D1、p27、TGF-β1在减黄促进肝再生的细胞周期调控机制中起到一定的作用,而p21可能不参与此调控.