竹节参总皂苷通过抑制NF-κB介导的炎性反应改善小鼠肿瘤恶病质研究  

Total saponins of Panax japonicus improve cancer cachexia in mice through inhibiting inflammatory response mediated by NF-κB

作　　者：周志勇[1] 陈亚昕[1] 李德鸿[1] 宋亚男[1] 张长城[1] 袁丁[2] ZHOU Zhi-yong;CHEN Ya-xin;LI De-hong;SONG Ya-nan;ZHANG Chang-cheng;YUAN Ding(College of Medical Sciences,China Three Gorges University,Yichang Hubei　443002,China;Dept of Pharmacy,Renhe Hospital,China Three Gorges University,Yichang Hubei　443000,China)

机构地区：[1]三峡大学医学院,湖北宜昌443002 [2]三峡大学仁和医院药剂科,湖北宜昌443000

出　　处：《中国药理学通报》2018年第4期532-537,共6页Chinese Pharmacological Bulletin

基　　金：湖北省自然科学基金创新群体项目(No 2013CFA014)

摘　　要：目的探讨竹节参总皂苷对小鼠结肠癌肿瘤恶病质的改善作用。方法 BALB/c小鼠皮下接种结肠腺癌CT26细胞建立恶病质模型,模型动物随机分为模型组、竹节参总皂苷低、高剂量组,接种后d 4开始灌胃给药,每日给药1次,正常与模型组给予10 mL·kg^(-1)生理盐水,低、高剂量组分别给予20、60 mg·kg^(-1)竹节参总皂苷干预,连续给药27 d后处理动物。观察竹节参总皂苷对恶病质小鼠体质量、胫骨前肌、腓肠肌、脾脏和附睾脂肪的影响;HE染色观察腓肠肌纤维横切面积的变化;流式微球试剂盒检测血清中炎性因子TNF-α和IL-1β的表达;Western blot检测腓肠肌与胫骨前肌中NF-κB、PAX7、MuRF1蛋白表达。结果与模型组相比,竹节参总皂苷能有效改善恶病质小鼠体质量下降(P<0.05),减少肌肉组织降解(P<0.05),同时竹节参总皂苷明显下调恶病质小鼠体内NF-κB表达,降低血清中IL-1β、TNF-α的水平(P<0.05)。结论竹节参总皂苷明显改善小鼠结肠癌恶病质状态,减少肌肉降解,其机制可能与抑制NF-κB介导的炎性因子表达相关。Aim To investigate the therapeutic effect of total saponins of Panax japonicus(SPJ)on cancer cachexia in mice with colon adenocarcinoma.Methods BALB/c mice were subcutaneously inoculated with murine colon adenocarcinoma CT26 cells to induce cachexia.The model animals were randomly divided into three groups:model group,SPJ low dose group and high dose group.Gavage started on the 4th day after inoculation,and the dosage regimen was as follows:the normal and model groups were given 10 mL·kg-1 saline,qd×27;the low dose and high dose groups were treated with 20 and 60 mg·kg-1 SPJ respectively,qd×27.After treatment,the effects of SPJ on body weight,tibialis anterior muscle,gastrocnemius muscle,spleen and epididymal fat changes of cachexia mice were observed.HE and Western blot were used to measure the changes of cross section of gastrocnemius muscle fibers and the expression of NF-κB,PAX7 and MuRF1 protein level in the gastrocnemius and tibialis anterior muscle.Results Compared with model group,the administration of SPJ could effectively reduce the weight loss(P<0.05),increase muscle mass(P<0.05)and decrease muscle tissue degradation in cachexia mice.Meanwhile,SPJ significantly reduced the levels of IL-1βand TNF-αin serum(P<0.05)and decreased the expression of NF-κB.Conclusion SPJ can improve cancer cachexia in mice in a dose-dependent manner.The potential mechanism may be associated with the inhibition of NF-κB mediated inflammatory factor expression.

关 键 词：竹节参总皂苷 肿瘤恶病质 肌肉代谢 脂肪降解 NF-ΚB途径 炎性反应 

分 类 号：R-332[医药卫生] R284.1