阿利吉仑改善小鼠肿瘤恶病质  

Aliskiren ameliorates cancer cachexia in mice

作　　者：王朝义[1] 王强[1] 郭敦伟 李聪[2] 郑曰勇[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 [2]重庆医科大学附属第一医院妇科,重庆400016

出　　处：《基础医学与临床》2016年第4期468-473,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81100399);重庆医科大学留学归国人员科研启动项目(2014年)

摘　　要：目的探讨阿利吉仑(Aliskiren,ASK)对肿瘤恶病质小鼠的影响及其可能的机制。方法 BALB/c小鼠随机分为对照组(Con)、肿瘤恶病质组(CA)及ASK干预组。经皮下接种小鼠结肠癌C26细胞建立肿瘤恶病质模型,ASK干预组于接种后第6、12天(AP和AT组)给予ASK 10 mg/(kg·d)灌胃。监测体质量、自发性活动及肿瘤生长情况。第20天收集标本,采用ELISA、比色法、real-time PCR和Western blot检测相关指标。结果 ASK能抑制肿瘤恶病质小鼠肿瘤生长,缓解体质量减轻,增加腓肠肌质量及其纤维横切面积和自发性活动。与Con组比较,CA组血清肾素、血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)水平及腓肠肌和血清TNF-α、IL-6水平明显升高(P<0.05),腓肠肌MDA含量升高、SOD及GSH-Px活性降低(P<0.05),Bnip3、LC3及Beclin1 mRNA和蛋白表达水平增加(P<0.05),LC3-Ⅱ/LC3-Ⅰ比值升高(P<0.05);AP和AT组经ASK干预后这些指标变化均得到缓解,且AP组效果优于AT组(P<0.05)。结论 ASK改善小鼠肿瘤恶病质的作用可能与阻断肾素血管紧张素系统进而抑制炎性反应、降低氧化应激水平和抑制自噬溶酶体途径有关。Objective To investigate the effect of ASK on cancer cachexia and its associated mechanism. Methods BALB / c mices were randomly assigned into control group（ Con）,cancer cachexia group（ CA） and ASK intervenient group. Murine colon adenocarcinoma C26 cells were inoculated subcutaneously into mices to induce cachexia. The ASK intervenient group was respectively gavaged with ASK 10 mg /（ kg·d） on day 6 and 12（ AP and AT group） after injection. Body weight,spontaneous activity and tumor growth were monitored daily. amples were collected on day 20 and ELISA,colorimetric method,Real-time PCR and Western blot were applied to examincorrelative indexes. Results ASK inhibited the growth of tumor,attenuated the loss of body mass,increased gastrocnemius weight and its myofiber cross-sectional area and spontaneous activity. Compared with Con group,the level of renin and angiotensinⅡ in serum,the level of TNF-α,IL-6 in serum and gastrocnemius of mice in CA group were significantly higther（ P〈0. 05）; The level of MDA in mice gastrocnemius of CA group was increased and the levels of SOD,GSH-Px were reduced（ P〈0. 05）; The mRNAs and protein expression of Binp3,LC3,Beclin1 in micegastrocnemius of CA group were upregulated,the ratio of LC3-Ⅱ / LC3-Ⅰwas increased（ P〈0. 05）. These indicator changes were attenuated by ASK in AT and AP group,and the effect of AP group was superior to that in AT group（ P〈0. 05）. Conclusions The effect of ASK alleviating cancer cachexia may be related to inhibitrennin-angiotensin system,thus reduce the oxidative and inflammatory burden,and which in turn suppress autophagy-lysosome pathway.

关 键 词：肿瘤恶病质 阿利吉仑 炎性反应 氧化应激 自噬溶酶体途径 

分 类 号：R730.5[医药卫生—肿瘤]