枸杞多糖通过诱导巨噬细胞极化抗胰腺癌的研究  

Anti-tumor effects of lycium barbarum polysaccharide on pancreatic cancer cells by polarization of macrophages

作　　者：杨青[1] 白光[2] 王巍[2] 包翠芬[1] 翟振华[2] 

机构地区：[1]辽宁医学院人体解剖与组织胚胎学教研室,辽宁锦州121000 [2]辽宁医学院附属第一医院

出　　处：《天津医药》2015年第11期1288-1291,I0005,共5页Tianjin Medical Journal

基　　金：吴阶平医学基金项目(320.6750.1281);辽宁省工业企业科技特派员行动项目

摘　　要：目的探讨枸杞多糖(LBP)通过诱导巨噬细胞极化成一型巨噬细胞(M1)抗小鼠胰腺癌细胞LTPA的功效。方法构建小鼠CB-17SCID皮下LTPA成瘤模型,随机分为荷瘤模型组(10只)及LBP治疗组(10只),LBP治疗组每日10 mg/kg LBP灌胃,荷瘤模型组每日同等剂量的生理盐水灌胃。将含有相同数量的小鼠巨噬细胞Raw264.7随机分为不同LBP浓度的实验组和对照组,MTT法检测各实验组与对照组中Raw264.7的光密度(OD)值;ELISA法检测LBP质量浓度为100 mg/L的实验组与对照组中Raw264.7分泌白细胞介素(IL)-12及IL-10的水平;流式细胞仪检测LBP质量浓度为100 mg/L的实验组与对照组中Raw264.7表面蛋白CD16/32及CD206的水平。小鼠荷瘤3周后剖瘤称质量并计算瘤体体积,检测LBP对皮下肿瘤生长的影响,HE染色和KI-67免疫组化法检测LBP对瘤组织镜下的改变及对LTPA增殖的影响。结果 100 mg/L LBP对Raw264.7的生长有明显促进作用(P<0.01),并使Raw264.7高表达CD16/32,低表达CD206;高分泌IL-12、低分泌IL-10。LBP治疗组瘤块质量、体积及KI-67的表达量显著低于荷瘤模型组(P<0.01),镜下肿瘤坏死区范围明显大于荷瘤模型组。结论 LBP能够通过诱导巨噬细胞极化成M1状态达到抗LTPA的作用。Objective To explore the effects of lycium barbarum polysaccharide （LBP） on restraining the mouse pancre？atic cancer cells LTPA by the polarization of macrophages to type 1 macrophages （M1）. Methods LTPA tumor model of the subcutaneous CB-17SCID mice was constructed. Model mice were randomly divided into tumor-bearing model group （n=10） and LBP treatment group （n=10）. The LBP treatment group was fed 10mg/kg LBP every day, and the tumor-bearing model group was fed the same dose of normal saline. The same amount of macrophages Raw264.7 was randomly divided into the control group and experimental groups （different concentrations of LBP）. MTT assay was used to detect the optical density （OD） of Raw264.7 in experimental groups and control group. ELISA was used to detect the levels of the interleukin （IL）-12 and IL-10 in experimental group （LBP was 100 mg/L） and the control group. Flow cytometry was used to test the levels of the membrane protein CD16/32 and CD206 in experimental group （LBP was 100 mg/L） and the control group. The tumor mass was weighted and the volume was calculated after three weeks. The effects of LBP on the growth of subcutaneous tumor were detected. HE staining and KI-67 staining were used to detect the microscopic changes of tumor and the proliferation of the LTPA. Results The dose of 100 mg/L LBP can promote the growth of the macrophages Raw264.7 （P〈0.01）, and induced the high expression of CD16/32 and low expression of CD206, high secretion of IL-12 and low secretion of IL-10. The weight, volume of the tumor and the expression of KI-67 were significantly lower in experimental group than those in the con？trol group （P〈0.01）. The microscopic necrosis area range of tumor was larger than that of control group. Conclusion The LBP has the effect of restraining LTPA by the polarization of macrophages to M1.

关 键 词：巨噬细胞 胰腺肿瘤 枸杞多糖 巨噬细胞极化 抗胰腺癌 1型巨噬细胞 2型巨噬细胞 

分 类 号：R285.5[医药卫生—中药学] R735.9[医药卫生—中医学]