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消水散对人肠癌小鼠腹腔移植模型B7/CD28/CTLA-4协同刺激通路及腹水微环境的影响
彭银花,彭 巍
0
(湖南省中医药研究院附属医院/湖南省中西医结合医院,湖南 长沙,410006)
摘要:
目的:研究消水散对人肠癌小鼠腹腔移植模型B7/CD28/细胞毒性T淋巴细胞相关抗原-4(CTLA-4)协同刺激通路及腹水微环境的影响。方法:采用腹腔注射人肠癌细胞株HCT116细胞建立人肠癌小鼠腹腔移植模型,分为模型组,消水散低、中、高剂量组,另设正常小鼠为对照组,每组各10只。观察阳虚症状积分,血清促肾上腺皮质激素(ACTH)、皮质醇(CORT)、三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺激素(TSH)含量,腹水量,瘤体积,瘤重,B7-1、B7-2、CD28、CTLA-4表达量及其mRNA表达水平,腹膜组织转化生长因子-β1(TGF-β1)、白细胞介素-10(IL-10)表达水平。结果:与正常组比较,模型组阳虚症状积分显著增加(P<0.01),ACTH、CORT、T3、T4、TSH含量显著降低(P<0.01)。与模型组比较,消水散呈剂量依赖性降低小鼠腹水量、瘤体积、瘤重、CTLA-4水平、TGF-β1、IL-10表达水平(P<0.05),增加B7-1、B7-2、CD28水平(P<0.05)。结论:消水散具有抗人肠癌移植瘤恶性腹水作用,这可能与抑制CTLA-4表达,促进T细胞激活,改善机体免疫抑制及腹腔免疫微环境有关。
关键词:  消水散  人肠癌小鼠腹腔移植模型  B7/CD28/细胞毒性T淋巴细胞相关抗原-4协同刺激通路  腹水微环境
DOI:
Effect of Xiaoshui powder on the B7/CD28/cytotoxic T lymphocyte-associated antigen 4 co-stimulation pathway and ascites microenvironment in a xenograft tumor mouse model of human colorectal cancer
PENG Yinhua,PENG Wei
(The Affiliated Hospital of Hunan Academy of Chinese Medicine/Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine,Changsha 410006,Hunan,China)
Abstract:
Objective:To investigate the effect of Xiaoshui powder on the B7/CD28/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) co-stimulation pathway and ascites microenvironment in a xenograft tumor mouse model of human colorectal cancer.Methods:An abdominal xenograft tumor mouse model of human colorectal cancer was established by intraperitoneal injection of human colorectal cancer HCT116 cells,and then the mice were divided into model group and low-,middle-,and high-dose Xiaoshui powder groups,while normal mice were established as control group,with 10 mice in each group.The above groups were observed in terms of the following indicators:the symptom score of Yang deficiency;the content of adrenocorticotropic hormone (ACTH),corticosterone (CORT),triiodothyronine (T3),thyroxine (T4),and thyroid stimulating hormone (TSH) in serum;ascites volume;tumor volume and tumor weight;the protein and mRNA expression levels of B7-1,B7-2,CD28,and CTLA-4;the expression levels of transforming growth factor-beta 1 (TGF-β1) and interleukin-10 (IL-10) in peritoneal tissue.Results:Compared with the control group,the model group had a significant increase in the symptom score of Yang deficiency (P<0.01) and significant reductions in the content of ACTH,CORT,T3,T4,and TSH (P<0.01).Compared with the model group,Xiaoshui powder reduced ascites volume,tumor volume,tumor weight,CTLA-4 level,and the expression levels of TGF-β1 and IL-10 (P<0.05) and increased the levels of B7-1,B7-2,and CD28 (P<0.05) in a dose-dependent manner.Conclusion:Xiaoshui powder can exert a therapeutic effect on malignant ascites due to the xenograft tumor of human colorectal cancer,possibly by inhibiting the expression of CTLA-4,promoting T cell activation,and improving immunosuppression and abdominal immune microenvironment.
Key words:  Xiaoshui powder  xenograft tumor mouse model of human colorectal cancer  B7/CD28/cytotoxic T lymphocyte-associated antigen 4 co-stimulation pathway  ascites microenvironment

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