艾灸对结肠炎相关性结肠癌大鼠P2X7受体、Wnt/β-catenin信号通路影响的研究  

Research on the Effects of Moxibustion on P2X7 Receptor and Wnt/β-catenin Signaling Pathway in Colitis-Associated Cancer Rats

作　　者：陆嫄[1,2] 顾沐恩 丁邦友 丁光宏[2] 郑寒丹[1] 李璟 马晓芃[1] 吴璐一[4] 李琪[3] 黄艳[1] 刘慧荣[1] 吴焕淦[1] LU Yuan;GU Mu-en;DING Bang-you;DING Guang-hong;ZHENG Han-dan;LI Jing;MA Xiao-peng;WU Lu-yi;LI Qi;HUANG Yan;LIU Hui-rong;WU Huan-gan(Shanghai Research Institute of Acupuncture and Meridian,Shanghai 200030,China;Fudan University,Shanghai 200433,China;Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Key Laboratory of Acupuncture-moxibustion and Immunological Effects,Shanghai University of Traditional Chinese Medicine,Shanghai 200030,China)

机构地区：[1]上海市针灸经络研究所,上海200030 [2]复旦大学,上海200433 [3]上海中医药大学附属岳阳中西医结合医院,上海200437 [4]上海中医药大学针灸免疫效应重点研究室,上海201203

出　　处：《上海针灸杂志》2020年第6期758-765,共8页Shanghai Journal of Acupuncture and Moxibustion

基　　金：国家自然科学基金项目(81574081,81873372);上海市卫生系统优秀人才培养计划(2018YQ11);上海市卫生和计划生育委员会科研课题(20184Y0106,20174Y0001);上海中医药事业发展三年行动计划项目[ZY(2018-2020)-CCCX-2004-01]。

摘　　要：目的观察艾灸对结肠炎相关性结肠癌(CAC)大鼠的干预作用,从嘌呤受体P2X7R与Wnt/b-catenin信号通路探讨可能的效应机制。方法将SD大鼠随机分为正常组、CAC组、隔药灸组、隔姜灸组。CAC组、隔药灸组、隔姜灸组均采用腹腔注射AOM联合DSS法制备CAC大鼠模型,隔药灸与隔姜灸组均取天枢(双)、气海穴进行治疗。记录各组大鼠体质量、疾病活动指数(DAI)和成瘤率;通过HE染色观察艾灸对CAC大鼠结肠损伤的干预效应;通过RT-q PCR和Western Blot技术,检测艾灸对CAC大鼠结肠组织C-myc、Wnt1、b-catenin、GSK-3bm RNA和P2X7R蛋白表达的调节作用。结果与正常组相比,CAC组大鼠体质量显著降低、DAI增高、成瘤率明显增加(P<0.05),结肠组织可见腺管共壁背靠背和筛样结构,高级别腺癌形成。CAC组大鼠结肠组织P2X7R蛋白表达显著下调(P<0.05),C-myc、b-catenin、GSK-3b、Wnt1 m RNA的表达均显著上调(P<0.05)。与CAC组相比,隔药灸组和隔姜灸组大鼠体质量增加,DAI降低(P<0.05),结肠组织P2X7R蛋白表达显著上调,C-myc m RNA下调(P<0.05);隔姜灸组成瘤率明显降低(P<0.05),且Wnt1、b-catenin、GSK-3bm RNA表达显著下调(P<0.05)。结论隔药灸、隔姜灸均能调节CAC大鼠结肠组织P2X7R及C-myc的异常表达,且隔姜灸还能下调CAC大鼠结肠组织Wnt1、b-catenin、GSK-3bm RNA的表达。Objective To observe the intervening effect of moxibustion on colitis-associated cancer(CAC)rats,for discussing the possible action mechanism based on P2X7 receptor(P2X7R)and Wnt/β-catenin signaling pathway.Method The Sprague-Dawley(SD)rats were randomized into a normal group,a CAC group,a herb-partitioned moxibustion(HPM)group and a ginger-partitioned moxibustion(GPM)group.The CAC,HPM and GPM groups all received intraperitoneal injection of AOM combined with DSS to develop CAC rat models.The HPM and GPM groups both selected bilateral Tianshu(ST25)and Qihai(CV6)points.Body weight,Disease Activity Index(DAI)and oncogenesis rate were recorded in each group;the intervening effect of moxibustion on colonic injury of CAC rats was observed by HE staining;real-time quantitative polymerase chain reaction(RT-qPCR)and Western Blot(WB)were used to detect the expressions of C-myc,Wnt1,β-catenin and GSK-3βmRNAs and P2X7R protein.Result Compared with the normal group,rats in the CAC group showed significant weight loss,and increases in DAI and oncogenesis rate(P<0.05),as well as glandular ducts with shared duct wall and back-to-back and sieve-like structures and the formation of advanced adenocarcinoma in colon tissues.The protein expression of P2X7R declined significantly(P<0.05)and the mRNA expressions of C-myc,b-catenin,GSK-3band Wnt1 increased significantly(P<0.05)in colon tissues of rats in the CAC group.Compared with the CAC group,rats in the HPM and GPM groups presented increased body weight,decreased DAI(P<0.05),significantly up-regulated protein expression of P2X7R and down-regulated mRNA expression of C-myc(P<0.05)in colon tissues;the oncogenesis rate was significantly lower in the GPM group(P<0.05),and the mRNA expressions of Wnt1,b-catenin and GSK-3bwere notably down-regulated(P<0.05).Conclusion HPM and GPM both can regulate the abnormal expressions of P2X7R and C-myc in colon tissues of CAC rats;GPM also can down-regulate the mRNA expressions of Wnt1,b-catenin and GSK-3bin colon tissues of CAC rats.

关 键 词：针灸疗法 灸法 结肠癌 结肠炎相关性 WNT/Β-CATENIN信号通路 P2X7R 药饼灸疗法 隔姜灸 大鼠 

分 类 号：R2-03[医药卫生—中医学]