适用于微创消融治疗研究的小鼠胰腺癌原位模型建立方法及比较  

Establishment and Comparison of Mouse Pancreatic Cancer Orthotopic Model for Minimally Invasive Ablation Therapy Study

作　　者：毛璐婧 张娜娜 刘昊 史爱华[2,3] 朱子语 吕毅[1,2,3,5] MAO Lujing;ZHANG Nana;LIU Hao;SHI Aihua;ZHU Ziyu;Lü Yi(Center for Regenerative and Reconstructive Medicine,Med-X Institute of the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 712000,China;National Local Joint Engineering Research Center for Precision Surgery&Regenerative Medicine,First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Shaanxi Province Center for Regenerative Medicine and Surgery Engineering Research,First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Health Science Center of Xi'an Jiaotong University,Xi'an 710061,China;Department of hepatobiliary surgery,First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院Med-X研究院再生与重建医学研究所,西安712000 [2]西安交通大学第一附属医院精准外科与再生医学国家地方联合工程研究中心,西安710061 [3]西安交通大学第一附属医院陕西省再生医学与外科工程研究中心,西安710061 [4]西安交通大学医学部,西安710061 [5]西安交通大学第一附属医院肝胆外科,西安710061

出　　处：《实验动物与比较医学》2022年第2期127-134,共8页Laboratory Animal and Comparative Medicine

基　　金：科技部重点研发计划项目:电磁声光耦合式无创消化道早癌陡脉冲电场消融系统研制(2018YFC0115300);国家自然科学基金-重大科学仪器研制项目:ERCP联合高压脉冲电厂微创肝胆胰肿瘤精准治疗工作站的研制(81727802)。

摘　　要：目的探究应用肿瘤细胞原位注射和肿瘤组织块移植法建立小鼠胰腺癌原位模型的优缺点,为以精准消融治疗研究为目的的小鼠胰腺癌原位模型的建立提供技术参考。方法取20只6~8周龄的健康雄性C57BL/6小鼠,分为4组,每组5只:A组采用小鼠胰腺癌Panc02细胞悬液直接注射法;B组采用含基质胶的小鼠胰腺癌Panc02细胞悬液注射法;C组采用小鼠胰腺癌组织块移植法;D组采用小鼠肿瘤组织块水凝胶粘接法。术后观察各组小鼠胰腺癌的成瘤率、肿瘤大小、腹腔脏器粘连程度和肿瘤转移情况,分别采用HE染色法和免疫组织化学法检测肿瘤组织形态学变化以及Ki67和α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)表达差异。结果A、B、C、D四组小鼠胰腺癌成瘤率分别为60%、80%、100%和100%。建模16 d后,A组小鼠肿瘤体积为(47.80±42.99)mm^(3),均质性差;B、C与D组小鼠肿瘤体积分别为(68.43±16.77)mm^(3)、(105.86±17.25)mm^(3)和(128.98±13.41)mm^(3),比A组明显增大(P<0.01),且均质性较好。A组小鼠腹腔重度粘连率为100%,B组重度粘连率为80%,C组与D组均未出现重度腹腔粘连。A组小鼠肿瘤转移率为100%,B组转移率为60%,C组与D组小鼠均未发现肿瘤转移。4组小鼠的肿瘤在组织学上无明显差异,且肿瘤组织中Ki67和α-SMA蛋白的相对表达水平差异无统计学意义(P>0.05)。结论采用肿瘤组织块移植法及水凝胶粘接法建立小鼠胰腺癌原位模型的成瘤率高,转移少,腹腔粘连轻,且未改变肿瘤细胞的生物学特性,易于操作和普及,造模效果更好。Objective To explore the advantages and disadvantages of orthotopic mouse model of pancreatic cancer established by orthotopic injection of tumor cells and transplantation of tumor tissue block,in order to provide technical reference for the establishment of orthotopic mouse model of pancreatic cancer with the purpose of precision ablation treatment.Methods A total of twenty healthy aged 6-8 weeks male C57BL/6 mice were divided into four groups,with five mice per group.Direct injection of mouse pancreatic cancer Panc02 cell was used in group A,direct injection of mouse pancreatic cancer Panc02 cell(containing matrigel)was used in group B,tumor tissue block transplantation of mouse pancreatic cancer was used in group C,the tumor tissue block hydrogel bonding method was used in group D.The tumor formation rate,tumor size,the degree of abdominal organ adhesion,tumor metastasis were observed after surgery in each group of mice.Tumor histomorphology and expressions of Ki67 andα-smooth muscle actin(α-SMA)protein were detected by HE staining and immunohistochemistry,repectively.Results The tumor formation rates in groups A,B,C,and D were 60%,80%,100%,and 100%respectively.After modeling for 16 d,the tumor volume of mice in group A was(47.80±42.99)mm^(3),with poor homogeneity.The tumor volume of mice in groups B,C and D[(68.43±16.77)mm^(3),(105.86±17.25)mm^(3),(128.98±13.41)mm^(3),respectively]was significantly larger than that in group A(P<0.01),with better homogeneity.The severe abdominal adhesion rate in group A mice was 100%and 80%in group B,and no severe abdominal adhesions occurred in groups C and D.The metastasis rate was 100%in group A and 60%in group B,and no tumor metastases were found in mice in groups C and D.There was no difference in the tumor formation of the four groups of mice,and no significant difference in the expression of Ki67 andα-SMA proteins in the tumor tissues(P>0.05).Conclusion The establishment of orthotopic pancreatic cancer in mice by tumor tissue transplantation and hydrogel adhesion

关 键 词：胰腺癌 原位模型 原位注射 肿瘤移植 小鼠 

分 类 号：Q95-33[生物学—动物学] R-332[医药卫生]