肝胰十二指肠联合切除对残肝再生和肝细胞生长因子,转化生长因子α、β表达的影响

Relationship between the Expression of HGF,TGF-α and TGF-β and Liver Regeneration after Hepatopancreatoduodenectomy in Rats

目的:探讨残肝再生和肝细胞生长因子(HGF)、转化生长因子α((TGF-α)和p(TGF-β)的表达。方法:30只SD大鼠随机分为2组:①组1为大部(68％)肝切除组,15只;②组2为大部(68％)肝叶切除加部分(50％)胰腺切除加近端十二指肠切除组。15只。每组3只大鼠,于术后12、24、48、72和168 h分别处死并采集肝脏样本,计算肝再生率。切除的肝脏组织用RT-PCR技术检测HGF、TGF-α及TGF-β在不同时间点的表达,并与免疫组化法检测的肝细胞增殖细胞核抗原(PCNA)进行对比研究。结果:组1残肝再生率逐步增加,至术后第7天达最高水平;PCNA峰值在术后24 h,随后逐步下降。HGF和TGF-α的表达在术后12 h逐渐增强,24 h达到高峰,随后逐渐下降,168 h时达最低水平,而TGF-β的表达在48 h时达高峰,然后下降。与组1相比,组2可显著减低残肝再生及PCNA峰值,并可显著减少肝细胞HGF、TGF-α及TGF-β的表达。结论:肝胰十二指肠联合切除可减低残肝再生反应,除了肝细胞自身分泌的HGF及TGF-α等细胞因子外,起源于胰腺和十二指肠的其他细胞因子亦可对肝细胞的增殖起调节作用。

Objective: To explore the expression of hepatocyte growth factor(HGF), transforming growth factor α (TGF-α) and transforming growth factor β ( TGF-β) during the process of hepatic regeneration in experimental animal model undergoing hepatectomy or simultaneous resection of hepar, pancreas and duodenum. Methods: Thirty SD rats were randomly divided into 2 groups: Ⅰ 68% hepatectomy group (Hx, n = 15);ⅡHx plus 50% pancreatectomy (Px) plus resection of proximal duodenum (Du) group (Hx + Px + du, n = 15). Every three rats of each group were killed for hepatic tissues collection on 12, 24, 48, 72 and 168 h after operations, while the hepatic tissues were obtained to detect the mRNA expression of HGF, TGF-α and TGF-P by semi-quantitative reverse transcript polymerase chain reaction (RT-PCR), and to observe the expression of compared with hepatic proliferation cell nuclear antigen (PCNA) by immunohistochemistry and hepatic regeneration rate (HRR). Results: The HRR increased gradually in Hx group, reaching its peak at 7th day after operation, while the highest peak of PCNA at 24 h. The expression of HGF and TGF-a increased gradually in Hx group, reaching its peak at 24 h followed by a decrease to the lowest level at 168 h. TGF-P expression rate increased to a peak level at 48 h. Compared with group 1, hepatopancreatoduodenectomy could decrease hepatic regeneration, PCNA and the expression of HGF, TGF-α and TGF-β. Conclusions: hepatopancreatoduodenectomy can reduce hepatic regeneration, which is correlated not only to the cytokines such as HGF and TGF-a secreted by hepatocyte, but also to other factors originated from pancreas and duodenum.