miRNA与大鼠肝癌肝移植模型术后肿瘤复发的相关性及意义
Relationship between miRNAs and recurrence of hepatocellular carcinoma after liver transplantation in Wistar rats and significance
目的 探讨微小RNA(miRNA)与肝癌大鼠肝移植术后肿瘤复发的相关性及意义.方法 将腹水型walker256癌肉瘤细胞注射入Wistar大鼠幼鼠腹腔,以培养和获取瘤细胞;将培养后含瘤细胞的腹水液注射到Wistar大鼠幼鼠腹股沟处,制备并获取皮下实体瘤组织块;将瘤组织块植入Wistar大鼠左外叶肝脏包膜下建立大鼠“种植性”肝癌模型,并于2周计算瘤块接种成瘤率;建立大鼠肝癌模型2周后,以肝癌大鼠为受鼠,建立同系大鼠肝移植模型.观察与记录术后3周内(21 d)受鼠的存活情况与肿瘤复发情况.术后21 d处死受鼠,切取移植肝组织,观察移植肝组织病理改变.术后21 d,将发生肿瘤复发的受鼠纳入复发组,未发生肿瘤复发的受鼠纳入未复发组,分别取两组肝组织和肝癌组织,采用实时定量聚合酶链反应法检测两组受鼠间miR-192、miR-122、miR-146a及miR-148a表达的差异.结果 瘤块接种成瘤率为100%,肝癌肝移植受鼠术后3周的累积存活率为76.5%.与未复发组受鼠相比,肝移植术后复发组受鼠肝组织中miR-192相对表达明显升高,miR-122、miR-146a和miR-148a的相对表达明显降低,两组比较,差异均有统计学意义(P<0.05).结论 肝癌肝移植术后肿瘤复发与未复发大鼠间miR-192、miR-122、miR-146a和miR-148a的表达水平存在差异,这些miRNA可能可以预测肝癌肝移植术后肿瘤复发.
更多Objective To investigate the relationship between miRNAs and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation in Wistar rats and the significance.Methods A small and superficial incision into the left lateral lobe of male Wistar rats was made.A 0.5-1.0 mm cube of walker-256 carcinosarcoma fragments was implanted into the liver incision.The rat model of HCC was established,and the liver transplantation model was established after 2 weeks.Three weeks after transplantation,the Wistar rats after liver transplantation were divided into 2 groups:no recurrence group (group A) and recurrence group (group B).The survival rate and recurrence were observed 3 weeks after liver transplantation.The liver tissues and HCC tissues in both two groups were obtained.The real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-192,miR-122,miR-146a and miR-148a in both two groups..Results The presence of solitary tumor was 100% at 2nd week in the intrahepatic tumor implantation model,and the orthotopic liver transplantation (OLT) of recipients was done.The 3-week cumulative survival rate after OLT was 76.5%.The relative expression of miR-192 was higher,and that of miR-122,miR-146a and miR-148a was lower in the recurrence group than in the non-recurrence group with the difference being statistically significant.Conclusion Our study,in addition to suggesting a different miRNA expression pattern between HCC samples of rats with recurrence and those with nonrecurrence,proposes miR-192,miR-122,miR-146a and miR-148a may serve as biomarkers for prognosis of HCC recipients following OLT.
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