Effects of moxibustion on the P2X7R/STAT3/VEGF pathway in rats with colitis-associated colon cancer  

艾灸对结肠炎相关性结肠癌大鼠P2X7R/STAT3/VEGF途径的影响

作　　者：Lin Ya-ying Wang Di Wu Huan-gan Gu Mu-en Li Qi Ma Zhe Huang Yan Lu Yuan Li Kun-shan Wu Lu-yi 林亚莹;汪迪;吴焕淦;顾沐恩;李琪;马喆;黄艳;陆嫄;李昆珊;吴璐一(Shanghai Research Institute of Acupuncture and Meridian,Shanghai 200030,China;Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Key Laboratory of Acupuncture and Immunological Effects,Shanghai University of Traditional Chinese Medicine,Shanghai 200030,China)

机构地区：[1]Shanghai Research Institute of Acupuncture and Meridian,Shanghai 200030,China [2]Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China [3]Key Laboratory of Acupuncture and Immunological Effects,Shanghai University of Traditional Chinese Medicine,Shanghai 200030,China

出　　处：《Journal of Acupuncture and Tuina Science》2021年第2期83-94,共12页针灸推拿医学（英文版）

基　　金：国家自然科学基金项目,No.81774405,No.81973953;上海市卫生和计划生育委员会科研课题,No.20174Y0001;上海市卫生和计划生育委员会卫生行业临床研究专项,No.20184Y0038,No.20184Y0106;上海市卫生系统优秀人才培养计划,No.2018YQ11;上海市自然科学基金课题,No.20ZR1453200。

摘　　要：Objective:To observe the effects of herb-partitioned moxibustion and ginger-partitioned moxibustion on the growth of colon tumors in rats with colitis-associated colon cancer(CACC),and explore the mechanism of moxibustion intervening CACC through the purinergic receptor P2X ligand-gated ion channel 7(P2X7R)/signal transducer and activator of transcription 3(STAT3)/vascular endothelial growth factor(VEGF)pathway.Methods:A total of 26 male Sprague-Dawley rats were selected.According to the random number table method,6 rats were selected as the normal group.The remaining 20 rats were injected intraperitoneally with azoxymethane(AOM)combined with oral dextran sodium sulfate(DSS)to prepare the CACC model.After the model was successfully established,2 rats were randomly selected for model identification.The remaining 18 rats which were successfully modeled were randomly divided into a model group,a herb-partitioned moxibustion group and a ginger-partitioned moxibustion group,with 6 rats in each group.Moxibustion intervention was performed in the herb-partitioned moxibustion group and the ginger-partitioned moxibustion group at Qihai(CV 6)and bilateral Tianshu(ST 25).Moxibustion was performed twice at each point each time,once a day,at a 1-day interval after 6 consecutive interventions,for a total of 30 interventions.After intervention,the colon tumor load,pathological change and histopathological score were observed.Immunohistochemistry was used to detect the expressions of VEGF,P2X7R,phospho-STAT3(p-STAT3),and nuclear factor-kappa B p65(NF-κB p65)proteins in rat colon tissue.Western blot was used to detect the levels of p-STAT3 and NF-κB p65 proteins in rat colon tissue.Results:Compared with the normal group,the colon tumor load and histopathological score in the model group were significantly increased(both P<0.001),and different grades of dysplasia were observed in colon tissue from the model group,reaching the degree of adenocarcinoma;the expression level of P2X7R protein in colon tissue was significantly decreas艾灸对结肠炎相关性结肠癌大鼠P2X7R/STAT3/VEGF途径的影响中文摘要:目的:观察隔药灸和隔姜灸对结肠炎相关性结肠癌(CACC)大鼠结肠肿瘤的影响,从嘌呤能离子通道型受体7(P2X7R)/转录激活因子3(STAT3)/血管内皮生长因子(VEGF)途径探讨艾灸干预CACC的效应机制.方法:选用Sprague-Dawley雄性大鼠26只,按照随机数字表法选择6只大鼠为正常组,其余20只采用腹腔注射氧化偶氮甲烷(AOM)结合葡聚糖硫酸钠(DSS)给药的方法制备CACC模型.造模后随机选择2只进行模型鉴定,其余18只造模成功的大鼠随机分为模型组、隔药灸组和隔姜灸组,每组6只.隔药灸组和隔姜灸组大鼠分别接受隔药灸和隔姜灸干预,两组均取气海和双侧天枢,每次每穴灸2壮,每日1次,连续干预6次后休息1 d,共干预30次.干预结束后,观察大鼠结肠组织瘤负荷和病理学改变,并进行病理学评分;采用免疫组化法检测结肠组织中VEGF、P2X7R、磷酸化STAT3(p-STAT3)和核因子κB p65(NF-κB p65)蛋白的表达;免疫印迹法检测结肠组织p-STAT3和NF-κB p65蛋白的表达.结果:与正常组比,模型组大鼠结肠组织瘤负荷增多,病理学评分显著升高(均P<0.001),结肠组织可见不同级别异型增生形成,达到腺癌程度;结肠组织P2X7R蛋白表达水平显著降低(P<0.001),p-STAT3、NF-κB p65和VEGF蛋白表达水平显著升高(均P<0.001).与模型组比,隔药灸组和隔姜灸组大鼠结肠组织瘤负荷减少,结肠组织病理学评分,p-STAT3、NF-κB p65及VEGF蛋白表达水平均显著降低(均P<0.05);结肠组织P2X7R蛋白表达水平显著升高(均P<0.05).结论:隔药灸和隔姜灸均能降低CACC大鼠结肠瘤负荷,延缓结肠组织腺瘤的进展;其机制可能与通过P2X7R/STAT3途径抑制STAT3磷酸化,进而降低VEGF蛋白表达有关.

关 键 词：Moxibustion Therapy Medicinal Cake-partitioned Moxibustion Ginger-partitioned Moxibustion Colitis-associated Neoplasms Vascular Endothelial Growth Factor Receptors Purinergic P2X7STAT3 Protein NF-kappa B 

分 类 号：R2-03[医药卫生—中医学]