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

作　　者：门昌君[1] 张国粱[1] 祖彩华 蔡金贞[3] 吴斌[3] 

机构地区：[1]天津市第一中心医院消化科,300192 [2]天津医科大学一中心临床学院 [3]天津市第一中心医院器官移植中心

出　　处：《中华器官移植杂志》2016年第6期357-361,共5页Chinese Journal of Organ Transplantation

基　　金：天津市卫生局科技基金面上项目（2014KY08）

摘　　要：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（21d）受鼠的存活情况与肿瘤复发情况。术后21d处死受鼠，切取移植肝组织，观察移植肝组织病理改变。术后21d，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。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 rniR-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 orthotopie 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.

关 键 词：大鼠 肝癌 肝移植 动物模型 微小RNA 复发 

分 类 号：R735.7[医药卫生—肿瘤] R-332[医药卫生—临床医学]