NCPP对肝纤维化作用及机理的初步研究  

Studies on Effects and Mechanism of the NCPP on Hepatic Fibrosis

作　　者：高尚先[1] 曲守方[1] 王群[2] 康国华[1] 宋静[2] 厉保秋[3] 张利宁[2] 

机构地区：[1]中国药品生物制品检定所,北京100050 [2]山东大学免疫学研究所 [3]山东大学毒理学研究所,济南250012

出　　处：《药物分析杂志》2005年第6期681-684,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:研究不同状态巨噬细胞分泌细胞因子及免疫功能的差异及无细胞短棒状杆菌纳米级制剂(NCPP)活化巨噬细胞在肝纤维化中的作用。方法:将 C57/B6小鼠分为痤疮丙酸杆菌(ATCC12930)组、NCPP 组及对照组。于第1d 及第7d 腹腔注射痤疮丙酸杆菌及 NCPP。第10d 处死小鼠,取腹腔液,分离培养巨噬细胞,收集上清液,用于检测 IFN-γ和 TNF-α。小鼠腹腔注射 NCPP 与痤疮丙酸杆菌,14d 后测定脾指数,并做脾病理检查。小鼠腹腔注射艾氏腹水癌细胞,于注射癌细胞前1d 及注射后次日起,连续(间隔1d)腹腔注射 NCPP 与痤疮丙酸杆菌5次,计算小鼠存活率。将猕猴分为对照组及 NCPP 高、中、低3个剂量组,肌肉内注射给药,每周2次,连续90d。剖取肝脏,做病理切片检查。结果:NCPP 组小鼠腹腔巨噬细胞产生的 IFN-r 水平明显高于痤疮丙酸杆菌组(p<0.05),TNF-α的水平明显低于痤疮丙酸杆菌组(p<0.05)。NCPP 组和痤疮丙酸杆菌组均引起小鼠脾脏明显增大,脾指数增高。病理检查两组脾脏均显示脾窦中单核细胞及多核巨细胞明显增多,但NCPP 组有明显的抑瘤作用,而痤疮丙酸杆菌组无明显抑瘤作用。猴肝病理结果显示 NCPP 高、中、低剂量组肝脏组织结构正常,未见明显的纤维化现象。结论:NCPP 和痤疮丙酸杆菌均可刺激单核巨噬细胞增生,但分泌的细胞因子及免疫功能有明显差异。NCPP 活化巨噬细胞未见明显致肝纤维化作用。Objective:To investigate the differences of macrophages on producing cytokines and immune function with different state and the effects of the NCPP(Nano-scale Product from Corynebacterium Parvum (CMCC65101))on hepatic fibrosis by Activating Macrophages.Methods:C57/B6 mice were divided into NCPP group,P acnes(ATCC12930) group and control group.At the dl and d7,NCPP and P.acnes were injected re- spectively ip At the d10,killed the mice and collected the liquid of peritoneal cavity.Separated and cultured the macrophages.Collected the supernatant fluid for IFN-gamma and TNF-alpha assay.Splenic index and Patholog- ic examination were measured at the day of 14 after mice were injected peritoneal with NCPP and P.acnes respec- tively.Ehrlich's ascites carcinoma cells were injected ip NCPP and P.acnes were given respectively in the same way the day before the injection and every other day there after for totally 5 times.The survival rate was figured out.Di- vided macaques into NCPP high-dose group、middle-dose group、low-dose group and control group.NCPP was given im injection,twice a week,for 90 days.Dissected the liver for slide.Results:Macrophages in the peritoneal cavity of mice in NCPP group produced,higher IFN-gamma(p<0.05)and lower TNF-alpha(p<0.05)than those in P.acnes group.NCPP group and P.acnes group induced the significant enlarging spleen and significant higher splenic index in the mice.Pathologic examination of the spleens Showed that there were significant increase of mon- ocyte and multinucleated giant cells in the splenic sinus in both groups.But NCPP group showed the significant effects in tumor inhibition.P.acnes group did not show the significant effects.Slide of macaques liver showed that liver tissue in NCPP high-dose group、mean-dose group and low-dose group were normal without the significant hepatic fibrosis.Conclusion:NCPP and P.acnes may stimulate mononuclear-phagocyte proliferation,but there are differences in producing cytokines and immune function of macrophages,NCPP don't induce significa

关 键 词：NCPP 纤维化作用 无细胞短棒状杆菌纳米级制剂 痤疮丙酸杆菌 步研究 小鼠腹腔巨噬细胞 活化巨噬细胞 艾氏腹水癌细胞 腹腔注射 机理 分泌细胞因子 巨噬细胞增生 免疫功能 病理检查 抑瘤作用 TNF-α IFN-γ 多核巨细胞 肝纤维化 

分 类 号：R978.7[医药卫生—药品] R135.2[医药卫生—药学]