从肠道菌群探讨艾灸“足三里”“肝俞”穴抑制裸鼠结肠癌细胞肝转移机制  

Exploring the Mechanism of Moxibustion at“Zusanli”and“Ganshu”Acupoints in Inhibiting Liver Metastasis of Colorectal Cancer Cells in Nude Mice from the Perspective of Gut Microbiota

作　　者：宋亚芳 张晓梅 蒋诗媛[2] 庄艺 王宇航 孙建华 SONG Yafang;ZHANG Xiaomei;JIANG Shiyuan;ZHUANG Yi;WANG Yuhang;SUN Jianhua(Acupuncture and Massage,Health Preservation and Rehabilitation of Nanjing University of Chinese Medicine,Nanjing 210023,China;Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;Changshu fifth People's Hospital,Changshu 215500,China)

机构地区：[1]南京中医药大学针灸推拿学院·养生康复学院,南京210023 [2]南京中医药大学附属医院,南京210029 [3]常熟市第五人民医院,常熟215500

出　　处：《世界科学技术-中医药现代化》2024年第12期3118-3126,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：和也健康科技有限公司重明鸟计划专项科研基金(HYCMP-2021005):穴位磁疗调控肝髓系巨噬细胞增强抗PD-1对抑制肠癌细胞肝转移治疗效应的机制研究,负责人:宋亚芳;国家自然科学基金委员会面上项目(82274630):GDNF-RET介导电针调节神经-结肠上皮对话缓解PIIBS模型小鼠内脏高敏感的机制研究,负责人:孙建华。

摘　　要：目的通过观察艾灸“足三里”、“肝俞”穴对抑制裸鼠结肠癌细胞肝转移肠道菌群的影响,探讨艾灸抑制结肠癌肝转移的潜在机制。方法运用脾脏注射法接种HCT116-GFP结肠癌细胞。将60只SPF级BALB/c雄性裸鼠分为4组:模型对照组、预防组、艾灸组、预防+艾灸组。穴位选用双侧“肝俞”和“足三里”穴,每天1次,每次10 min。计算各组间成瘤率及肝转移率、转移灶数目,运用16S rRNA法检测肠道菌群多样性变化。结果艾灸可显著降低肝转移率,减少转移灶数目。与模型对照组相比,预防组罗伊氏乳杆菌、Robinsoniella_peoriensis显著降低(P<0.05);艾灸组乳酸杆菌显著降低,耳蜗形梭菌、丹毒丝菌属-多枝梭菌显著升高(P<0.01);预防+艾灸组乳酸杆菌显著降低,丹毒丝菌属-多枝梭菌、嗜黏蛋白阿克曼菌、耳蜗形梭菌显著升高(P<0.05)。LEfSe差异分析显示预防组以粪芽孢菌属改变为主;艾灸组以Muribaculaceae、丹毒丝菌为标志;预防+艾灸组以疣微菌门、嗜黏蛋白阿克曼菌、丹毒丝菌为标志。结论艾灸“足三里”“肝俞”穴可抑制裸鼠结肠癌细胞肝转移,尤其给予5周的造模前后艾灸干预,抑制肝转移效果最好,其机制可能与调节肠道微生物群失衡状态有关。Objective To observe the effect of moxibustion of“Zusanli”and“Ganshu”on the intestinal flora of colorectal cancer cells liver metastasis in nude mice and its possible mechanism was explored.Methods HCT116-GFP colon cancer cells were inoculated by spleen injection,sixty SPF BALB/c male nude mice were divided into model control group,Pre-Mox group,Post-Mox group,Pre-Post-Mox group.Bilateral“Ganshu(BL18)”and“Zusanli(ST36)”acupoints were selected for moxibustion intervention for once a day for 10 minutes each time.the tumor formation rate,liver metastasis rate and the number of tumor of each group were calculated.Furthermore,16S rRNA analysis was used to assess their microbial diversity.Results Moxibustion intervention can significantly reduce the rate of liver metastasis,reduce the number of metastatic foci.Compared with the model control group,Lactobacillus_reuteri and Robinsoniella_peoriensis were significantly lower in Pre-Mox group(P<0.05).Lactobacillus_gasseri decreased significantly,Clostridium_cocleatum and Erysipelatoclostrdum_ramosum multiplex increased significantly in the Post-Mox group(P<0.01).Pre-Post-Mox mice had significantly decreased levels of Lactobacillus_gasseri,and Clostridium_cocleatum,Akkermansia_muciniphila and Clostridium_cocleatum were significantly increased(P<0.05).LEfSe Difference analysis showed that the Pre-Mox group was mainly changed by Coprobacillus;the Post-Mox group was marked by Muribaculaceae and erysipelas;the Pre-Post-Mox group took Verrucomicrobia,Akkermansia_muciniphila and erysipelas as signs.Conclusion Moxibustion could exert an inhibitory effect on CRC liver metastasis,especially the 5-week Pre-PostMox treatment showed the best inhibitory.The potential mechanism might rely on the alteration of microbiota diversity and composition.

关 键 词：艾灸 经脾注射法 结肠癌肝转移 肠道菌群 

分 类 号：R285.5[医药卫生—中药学]