薏苡附子败酱散联合电针治疗对AOM/DSS小鼠炎症相关性结直肠癌的防治作用及机制

Effect and mechanism of Yiyi Fuzi Baijiang San combined with electroacupuncture on colitis-associated colorectal cancer in AOM/DSS mice

目的:探究薏苡附子败酱散(Yiyi Fuzi Baijiang San,YYFZBJS)联合电针(electroacupuncture,EA)对AOM/DSS模型小鼠炎症相关性结直肠癌(colitis-associated colorectal cancer,CAC)的防治作用及对结直肠癌上皮间质转化(epithelial-mesenchymal transition,EMT)相关蛋白表达情况的影响。方法:建立AOM/DSS诱导的CAC小鼠模型,将40只小鼠随机分为模型组、针药结合组、薏苡附子败酱散组、电针组和阿司匹林组,于实验第2周开始干预治疗,治疗过程中记录各组小鼠一般情况,统计体质量变化、疾病活动指数(disease activity index,DAI)评分及生存情况,于实验末比较各组小鼠结直肠长度、成瘤数量及肿瘤大小,通过HE染色观察结直肠组织及肿瘤组织的病理变化,免疫组织化学染色观察结直肠肿瘤Ki-67、PCNA、p-NF-κB、NF-κB、E-cadherin、ZO-1、Occludin、Vimentin和N-cadherin蛋白的表达。结果:与模型组相比,针药结合组小鼠体质量显著升高(P<0.05),DAI分值降低(P<0.05),生存率为87.5%,结直肠长度显著增加(P<0.01),直径小于2 mm的肿瘤数量减少(P<0.05),直径介于2~4 mm之间和大于4 mm的肿瘤数量显著减少(P<0.01),总成瘤数量明显下降(P<0.01),结直肠形态明显改善;肿瘤组织病理评分降低(P<0.01),肿瘤组织中Ki-67、PCNA、p-NF-κB、NF-κB、Vimentin和N-cadherin蛋白表达量降低(P<0.01),E-cadherin、ZO-1和Occludin蛋白表达量升高(P<0.05)。结论:薏苡附子败酱散联合电针对AOM/DSS模型小鼠的CAC发生发展有防治作用,其机制可能与下调NF-κB信号通路,减缓EMT进程有关。

Objective:To explore the preventive and therapeutic effect of Yiyi Fuzi Baijiang San(YYFZBJS)combined with electroacupuncture(EA)on AOM/DSS colitis-associated colorectal cancer(CAC)model mice and the effect on the expression of colorectal cancer epithelial-mesenchymal transition(EMT)related proteins.Methods:The CAC mouse model was established through AOM/DSS.Forty mice were randomly divided into model group,YYFZBJS+EA group,YYFZBJS group,EA group and aspirin group.The intervention treatment was started in the second week of the experiment.During the treatment,the general condition of mice in each group was recorded,and the body mass change,disease activity index(DAI)score and survival rate were counted.At the end of the experiment,the colorectal length,number of tumors and tumor size of mice in each group were compared.HE staining was used to observe the pathological changes of colorectal tissues and tumor tissues,and immunohistochemical staining was used to observe the expression of Ki-67,PCNA,p-NF-κB,NF-κB,E-cadherin,ZO-1,Occludin,Vimentin and N-cadherin in colorectal tumors.Results:Compared with the model group,the body weight of the mice in YYFZBJS+EA group increased significantly(P<0.05),the DAI score decreased(P<0.05),the survival rate was 87.5%,the length of the colon and rectum increased significantly(P<0.01),the number of tumors with a diameter of less than 2 mm decreased(P<0.05),the number of tumors with a diameter of 2~4 mm and more than 4 mm decreased significantly(P<0.01),the number of total tumors decreased significantly(P<0.01),and the morphology of the colon and rectum improved significantly.The histopathological score of tumor tissues decreased(P<0.01).The expression of Ki-67,PCNA,p-NF-κB,NF-κB,Vimentin and N-cadherin in tumor tissues decreased(P<0.01),and the expression of E-cadherin,ZO-1 and Occludin increased(P<0.05).Conclusion:Yiyi Fuzi Baijiang San combined with electroacupuncture could prevent CAC development in AOM/DSS model mice,and its mechanism might be related to down-regulating NF-κB signaling pathway and slowing down EMT process.