泮托拉唑改善小鼠肿瘤恶病质骨骼肌消耗  

Effect of Pantoprazole on Skeletal Muscle Loss in a Mouse Model of Cancer Cachexia

作　　者：郭敦伟 王朝义[1] 王强[1] 乔忠鹏 游松[1] 唐华[1] 

机构地区：[1]重庆医科大学附属第一医院胃肠外科,重庆400016

出　　处：《中山大学学报（医学科学版）》2017年第2期254-259,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：重庆市研究生科研创新项目(CYS15135)

摘　　要：【目的】研究泮托拉唑对肿瘤恶病质骨骼肌消耗的缓解作用。【方法】将24只BALB/c小鼠随机分为3组,分别为正常组(NN)、恶病质组(CC)、干预组(PPI),每组8只。荷瘤小鼠采用腋下接种小鼠结肠癌细胞(c26),建立肿瘤恶病质模型。每日监测各组小鼠体质量、肿瘤大小及精神毛发等一般情况。接种后第12天干预组采取泮托拉唑灌胃,其余组采取生理盐水灌胃。干预后第12天处死小鼠收集标本。称量腓肠肌及肿瘤质量,测量肿瘤大小,HE染色观察骨骼肌形态变化,血清ELISA法检测IL-6、TNF-α水平,qRT-PCR和Werstern blot分别检测腓肠肌MuRF1、MAFBx、Myod1和myf5的mRNA和蛋白表达水平。【结果】与CC组相比,PPI组小鼠及腓肠肌质量分别增加39.8%和24.2%,腓肠肌纤维横切面积增加25.4%;PPI组Myod1和myf5的mRNA水平及蛋白表达水平明显高于CC组(P<0.05);PPI组血清IL-6及TNF-α水平较CC组分别降低30.7%和18.9%;PPI组MuRF1、MAFBx蛋白表达水平明显低于CC组(P<0.05)。【结论】泮托拉唑对肿瘤恶病质骨骼肌消耗具有保护作用,其机制可能与抑制炎症及泛素蛋白酶体途径(UPS),上调生肌调节因子(MRF)有关。【Objective】To investigate the effect of pantoprazole on skeletal muscle wasting in cancer cachexia and the possible mechanism.【Methods】24 male BALB/c mice were randomly divided into control group（NN）,cancer cachexia group（CC）,pantroprazole treatment group（PPI）.The mice in CC and PPI were inoculated subcutaneously with mouse colon adenocarcinoma C26 cells to establish a model of cancer cachexia.The mice in PPI group were gavaged with 75 mg/kg pantoprazole dissolving in physiological saline,while those in NN and CC group were gavaged with 0.1 mL/10 g physiological saline.The mice were killed 12 d after treatment.The weight of gastrocnemius and tumour and the size of tumour were measured.The morphological change of skeletal muscle were evaluated by the method of stain with hematoxylin and eosin（HE）.The levels of IL-6 and TNF-α in serum were tested by ELISA.q RTPCR was used to assess the expression of mRNA of Myod1 and myf5 in skeletal muscle.The protein expressions of MuRF1,MAFBx,Myod1 and myf5 were measured by Western blot.【Results】Compared with CC group,pantoprazole can increase the weight of mice and gastrocnemius（39.8% and 24.2%,respectively）,cross section area（25.4%）,levels of mRNA and protein of Myod1 and myf5（P〈0.05）,while the levels of IL-6 and TNF-α decreased（30.7% and 18.9%,respectively）,as well as the levels of protein expression of MuRF1 and MAFBx（P〈0.05）.【Conclusion】Pantoprazole can attenuate the wasting of skeletal muscle,the potential mechanism may be related to the inhibition of inflammatory factors and UPS,and up-regulation of Myod1 and myf5.

关 键 词：泮托拉唑 肿瘤恶病质 炎症 泛素蛋白酶体途径 生肌调节因子 

分 类 号：R730.5[医药卫生—肿瘤]