肝癌切除术后转移过程中炎性递质的作用

Effects of inflammatory cytokines on metastasis of liver cancer after apparently curative operation

目的:探讨炎性细胞因子在肝癌术后复发过程中的影响. 方法:615小鼠脾包膜下接种肝癌H22腹水瘤细胞,同时进行2/3肝切除(PH)或假手术(Sham),术后不同时间采集肝脏标本提取mRNA,测定肝组织中TNF-α,IL-1β,IL-6 和VCAM-1的表达水平.为观测肝内肿瘤转移程度,动物被饲养11 d,断颈处死,计数肝脏表面瘤结节数量. 结果:PH组与假手术组比较,接受肝切除的动物肝内转移瘤明显增多,两组间比较具有显著性差异(P=0.00 087). 肝组织内TNF-α、IL-1β、IL-6和VCAM-1 mRNA 的表达明显增高,其峰值分别在96、72、48和72 h.其中TNFαmRNA在PH后4 h迅速升高,在术后4 d内升高呈线性关系.IL-1β在术后72 h达到峰值后迅速降至正常水平.IL-6 mRNA表达的峰值时间为PH后48 h, 下降至正常水平的时间也较迅速.VCAM-1 mRNA的表达在正常组织含量甚微,几乎观测不到,但在术后升高有两个峰值,分别为4和72 h,可达到正常水平3-6倍. 结论:炎性细胞因子,尤其是TNF-α的表达与转移瘤有明显的正相关,可能对肿瘤转移有一定的增强效果.

AIM: To explore the effects of relevant inflammatory cytokines on the metastasis of liver cancer after apparently curative operation. METHODS: A mouse model for metastasis of experimental liver cancer was established by inoculation of hepatoma 22 (H22) cells into subserous layer of spleen. Partial hepa-tectomy (PH) or sham operation (SH) was performed at various periods of spleen inoculation, and metastasis was observed at the 11th day. The expression levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1), were measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The metastatic tumors were significantly increased in PH mice as compared with those in SH mice (stage Ⅳ: 16/40 vs 4/38, P= 0.00 087) and the mRNA expression of TNF-α, IL-1β, IL-6 and VCAM-1 were markedly higher. The peak of TNF-α, IL-1β, IL-6 and VCAM-1 expression were observed 96, 72,48 and 72 hours after inoculation, respectively. Among them, TNF-α expression was found rapidly increased 4 hours after PH, and then linearly increased till 96 hours. The concentrations of IL-1β and IL-6 fell quickly to normal level after peaks. The peak expression of VCAM-1 appeared twice (at 4 and 72 h) after PH, which was 3-6 times higher than normal level. CONCLUSION: The levels of inflammatory cytokines, especially TNF-α, are positively related to the metastasis, and they may promote the metastasis of liver cancer.