ChRM3对胆管癌神经浸润的影响  

EFFECT OF CHRM3 ON THE PERINEURAL INVASION OF CHOLANGIOCARCINOMA

作　　者：范帅 赵伟[1] 王国磊 魏宗强 窦蓉蓉[1] 张炳远[1] FAN Shuai, ZHAO Wei, WANG Guolei, WEI Zongqiang, DOU Rongrong, ZHANG Bingyuan(Department of Hepatobiliary Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Chin)

机构地区：[1]青岛大学附属医院肝胆外科,山东青岛266003 [2]青岛大学附属医院崂山院区业务部,山东青岛266003

出　　处：《精准医学杂志》2018年第3期263-266,共4页Journal of Precision Medicine

基　　金：山东省科技发展计划项目(2011GGB14010)

摘　　要：目的探讨毒蕈碱型乙酰胆碱受体M3(ChRM3)对胆管癌神经浸润的影响。方法采用免疫组织化学方法检测60例胆管癌组织及30例正常胆管组织中ChRM3的表达水平;建立小鼠背根神经节(DRG)与胆管癌细胞RBE体外共培养模型,并加入ChRM3激动剂(匹罗卡品)及其拮抗剂(阿托品),通过观察神经纤维的生长和胆管癌RBE细胞对DRG和周围神经纤维的黏附及浸润,检测ChRM3在匹罗卡品和阿托品作用下对胆管癌RBE细胞浸润DRG及周围神经纤维的影响。结果 ChRM3在胆管癌组织中的阳性表达率高于正常胆管组织,差异有统计学意义(P<0.01)。神经浸润在胆管癌中发生率为91.7%(55/60)。DRG-RBE细胞共培养模型中加入匹罗卡品后,RBE细胞浸润DRG及周围神经纤维的细胞数明显增加,差异有统计学意义(P<0.05),这种作用在加入阿托品后明显减弱,差异有统计学意义(P<0.05)。而将阿托品单独作用于胆管癌组织,神经浸润结果与对照组比较无明显差异(P>0.05)。结论 ChRM3参与了胆管癌神经浸润过程,可能为抑制胆管癌的神经浸润提供了新治疗靶点。Objective To explore the effect of muscarinic acetylcholine receptor M3（ ChRM3） on the perineural invasion of cholangiocarcinoma（ CLC）. Methods Immunohistochemistry was used to detect the expression of ChRM3 in 60 CLCtissues and 30 normal bile duct tissues. A co-culture model of mouse dorsal root ganglia（ DRG） and human CLC cell line RBE was established. The ChRM3 agonist pilocarpine and the ChRM3 antagonist atropine were added into the co-culture model to observe the growth of nerve fibers and the adhesion and invasion of RBE cells into the DRG and surrounding nerve fibers and to evaluate the effect of ChRM3 on the invasion of RBE cells into the DRG and surrounding nerve fibers. Results The positive rate of ChRM3 was significantly higher in the CLC tissues than in the normal bile duct tissues（ P〈0.01）. The perineural invasion rate reached 91.7%（ 55/60） in the CLC tissues. The number of RBE cells invading the DRG and surroundingnerve fibers was significantly increased after pilocarpine was added to the co-culture model（ P〈0.05）. This effect was significantly weakened after atropine was added to the co-culture model（ P〈0.05）. However,there was no significant change in the perineural invasion when atropine alone was added to the co-culture model（ P〈0.05）. Conclusion ChRM3 is involved in the perineural invasion of CLC cells,which may provide a new therapeutic target to inhibitthe perineural invasion of CLC.

关 键 词：胆管肿瘤 受体 毒蕈碱M3 肿瘤浸润 神经系统 体外研究 

分 类 号：R735.8[医药卫生—肿瘤]