三物白散通过影响FXR表达逆转Th1/Th2漂移发挥抗肝癌免疫应答作用  

Sanwubai Powder Reversing Th1/Th2 Drift by Affecting FXR Expression and Exerting Anti-liver Cancer Immune Response

作　　者：李素素 濮文渊[1] 凌云[1] 马俊杰[1] 孙松娴[1] 张静远[1] 周春祥[1] LI Susu;PU Wenyuan;LING Yun;MA Junjie;SUN Songxian;ZHANG Jingyuan;ZHOU Chunxiang(Nanjing University of Chinese Medicine,Nanjing Jiangsu China 210046)

机构地区：[1]南京中医药大学,江苏南京210046

出　　处：《中医学报》2021年第5期1021-1028,共8页Acta Chinese Medicine

基　　金：国家自然科学基金项目(81774021);江苏省高等学校自然科学研究项目(19KJB360003)。

摘　　要：目的:探讨三物白散干预肝癌原位移植瘤小鼠Th1/Th2细胞因子水平、回肠组织中法尼醇X受体(farnesoid X receptor,FXR)的表达及其和肠道菌群间的关系。方法:将ICR小鼠随机分为5组,即空白组、模型组、三物白散(56.47 mg·kg^(-1))组、万古霉素(5 mg·kg^(-1))组、消胆胺(2%消胆胺饲料)组,除空白组外,其余组采用肝内注射H22细胞复制肝癌模型,连续给药3周后,HE染色观察肿瘤细胞病理变化;ELISA法检测小鼠血清和肝脏组织中白细胞介素-2(interleukin-2,IL-2)、白细胞介素-4(interleukin-4,IL-4)、白细胞介素-10(interleukin-10,IL-10)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和干扰素-γ(interferon-gamma,IFN-γ)水平;运用q-PCR和Western Blot法检测小鼠回肠组织中FXR的表达;通过16S rRNA法检测小鼠肠道菌群表达。结果:与模型组比较,三物白散组和万古霉素组Th1细胞因子IL-2、TNF-α和IFN-γ水平升高,Th2细胞因子IL-4和IL-10水平降低;回肠组织FXR表达降低;肠道中梭状芽孢杆菌丰度降低。结论:三物白散可能通过调节肠道菌群结构,下调回肠组织FXR的表达,逆转Th1/Th2漂移,发挥抗肝癌免疫应答作用。Objective:To explore the relationship between the Th1/Th2 cytokine levels,the expression of farnesoid X receptor(FXR)in the ileum tissue and the intestinal flora after the intervention of Sanwubai Powder in mice with orthotopic transplantation of liver cancer.Methods:ICR mice were randomly divided into 5 groups,namely blank group,model group,Sanwubai Powder(56.47 mg·kg^(-1))group,vancomycin(5 mg·kg^(-1))group,cholestyramine(2% cholestyramine feed)group.Except for the blank group,the other groups used intrahepatic injection of H22 cells to replicate the liver cancer model.After continuous administration for 3 weeks,the growth of tumor cells was observed by HE staining.ELISA method is used to detect the levels of interleukin-2(IL-2),interleukin-4(IL-4),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and interferon-gamma(IFN-γ)in mouse serum and liver tissue.Q-PCR and Western Blot methods were used to detect FXR expression in mouse ileum;16 S rRNA technology was used to detect mouse intestinal flora expression.Results:Compared with the model group,the levels of Th1 cytokines IL-2,TNF-α and IFN-γ increased in the Sanwubai Powder group and the vancomycin group,while the levels of Th2 cytokines IL-4 and IL-10 decreased;the expression of FXR in the ileum tissue decreased,and the abundance of Clostridium in the intestinal flora decreased.Conclusion:Sanwubai Powder can regulate the structure of intestinal flora,down-regulate the expression of FXR in ileal tissue,reverse Th1/Th2 drift,and exert an immune response against liver cancer by regulating the structure of intestinal flora.

关 键 词：三物白散 肝癌 法尼醇X受体 肠道菌群 

分 类 号：R285.5[医药卫生—中药学]