Abstract:

Objective In order to explore the influence of liver regeneration on tumor recurrence after partial hepatectomy as well as the possible mechanisms. Methods Portal vein injection of 256 tumor cells suspension after partial hepatectomy was performed to simulate the tumor recurrence and metastasis . The animals were divided into three groups（H0 group， H30 group and H70 group）according to different proportion of hepatectomy. The rate of tumor recurrence， change in body weight， tumor-bearing graft weight， tumor-bearing graft to body weight ratio were comparedamong three groups after three weeks. Meanwhile， the accumulate abundance of protein CAPNS-1 and the PCNA index were utilized to judge the tumor invasiveness. Western Blot and RT-PCR analyses were applied respectively to assess the abundance of protein c-met， VEGFR-2 and mRNA. Moreover， the relation between the tumor invasiveness and the abundance of c-met，VEGFR-2 were explored. Results All rats in H70， H30 and H0 groups were alive after 3 weeks with metastatic tumor lesions in their livers. The extent of increase or decrease in general indexes， such as body weight，tumor-bearing graft weight and tumor-bearing graft to body weight ratio， were obviously in group H70. And the tumors in rats of group H70 revealed upper invasiveness and malignant potential. In addition， the H70 group displayed diffuse distribution of tumors. The level of CAPNS-1 expression and the PCNA index were evaluated in H70. The largest resection was also associated with significant up-regulation of c-met， VEGFR-2 protein and mRNA expression. Furthermore， there was a significantly correlation between the level of VEGFR-2， c-met and the change in general indexes， and the level of CAPNS-1 protein expression. Conclusion This research reveals that liver regeneration after partial hepatectomy not only can accelerate the malignant transformation， but also can promote tumor growth. 

Key words:

Living donor liver transplantation ； , Partial hepatectomy ； , Hepatocellular carcinoma ； , Liver regeneration； , Tumor recurrence

摘要：

目的 探索肝部分切除术后肝再生过程是否影响肿瘤复发，并探究其可能存在的发生机制。方法 在切除不同肝比例基础上，即无肝切组、30% 肝切组、70% 肝切组，将 Walker 256 肿瘤细胞悬液经门静脉注射，模拟肝癌肝部分切除术后的肿瘤转移复发。观测术后 3 周不同比例肝切组一般观察指标（大鼠体重变化、肿瘤复发率、荷瘤肝重以及肝体质量比等），分析肝再生对于肿瘤复发的作用。WesternBlot 用于分析肿瘤组织中的 CAPNS-1 蛋白表达水平，同时 PCNA 指数采用免疫组化染色测定，进一步分析判断肿瘤组织的侵袭性。此外，Western Blot 和 RT-PCR 分别用于观测肿瘤组织中 VEGFR-2、c-met 蛋白和 mRNA 转录丰度，判断 VEGFR-2、c-met 的转录水平是否与肿瘤组织的生长、浸润相关。结果 术后3 周不同比例肝切除实验大鼠皆存活，且均表现出转移性肿瘤结节。70% 肝切实验组术后 3 周大鼠的体重变化，荷瘤肝体质量比以及荷瘤肝重显著高于无肝切组、30% 肝切组（P ＜ 0.05）。Western Blot 与免疫组化染色实验结果表明 70% 肝切实验组大鼠肿瘤组织中的 CAPNS-1 表达以及 PCNA 指数明显上升（P ＜ 0.05）。 Western Blot、RT-PCR 结果分别表明，70% 肝切组实验大鼠肿瘤组织中 c-met、VEGFR-2 的蛋白表达水平 和 mRNA 转录丰度比其他实验组增加幅度大（P ＜ 0.05），且 VEGFR-2、c-met 的表达量与实验大鼠的体重变化、CAPNS-1 表达、荷瘤肝重、荷瘤肝体质量比之间显著相关。结论 肝部分切除手术完成后肝再生过程不仅加速了肿瘤组织的生长，还促进了其恶性转换，这可能是由肝再生过程中生成的细胞因子引起的。

关键词:

亲体肝移植 , 肝部分切除 , 肝细胞肝癌 , 肝再生 , 肿瘤复发