钙蛋白酶抑制剂、α-硫辛酸单用及联用治疗癌性恶病质  

Caplain inhibitor and α-lipoic acid used alone or in combination for cancer cachexia

作　　者：陈思曾[1] 曹少祥[2] 

机构地区：[1]福建医科大学附属第一医院胃肠外科,福州350005 [2]福建医科大学第一临床医学院

出　　处：《中华实验外科杂志》2013年第8期1668-1671,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81272465）

摘　　要：目的探讨钙蛋白酶（caplain）抑制剂ALLN（N-acetyl-Leu-Leu-Norleucinal）、α-硫辛酸（α-LA）单用及联用对癌性恶病质小鼠的治疗效果及其机制。方法结肠腺癌Colon26（C26）细胞接种于小鼠前腋窝皮下构建恶病质模型。药物干预7d后检测去瘤体质量、腓肠肌湿重、血生化、细胞因子水平、丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、肿瘤组织核因子-κB（NF-κB）表达及骨骼肌中caplain-1和泛素mRNA表达。结果荷瘤对照组caplain-1与泛素mRNA表达值分别为0．84±0．10、2．68±0．08，ALLN组、α-LA组、ALLN＋α-LA组caplain-1表达值分别为0．59±0．07、0．65±0．07、0．57±0．04，泛素mRNA表达值分别为2．29±0．07、2．34±0．05、2．20±0．10，均低于荷瘤对照组（P〈0．05），其他指标亦有不同程度的改善（P〈0．05）。结论caplain抑制剂和α-硫辛酸均具改善癌症恶病质的作用，两者联合应用效果更好。Objective To study the treatment effects by using ealpain inhibitor N-acetyl-Leu-Leu- Norleucinal （ALLN） and α-lipoic acid （α-LA） alone or in combination for mice with cancer cachexia and the possible mechanism. Methods Murine colon 26 adenocarcinoma cells were inoculated subcutaneously into the anterior subaxilla of Balb/c mice to establish cachexia model. Tumor-free body weight and wet weight of gastrocnemius were measured, and the levels of serum biochemistry parameters, cytokines, ma- londialdehyde （MAD） , superoxide dismutase （SOD） , nuclear factor-κB （NF-κB） , caplain-1 and ubiq- uitin mRNA in skeletal muscle were detected at 7th day after intervention. Results The absorbance （A） ratio of calpain-1 and ubiquitin mRNA in tumor-bearing control group was 0. 84 ± 0. 10 and 2. 68 ± 0. 08, that of ealpain-1 in ALLN group,α-LA group and ALLN ± α-LA group was 0. 59 ±0. 07, 0. 65 ±0. 07 and 0. 57 ± 0. 04, and that of ubiquitin mRNA in ALLN group, α-LA group and ALLN ＋α-LA group was 2. 29 ± 0. 07, 2. 34 ± 0. 05 and 2. 20 ± 0. 10, respectively. The A ratio of ealpain-1 and ubiquitin mRNA in ALLN group, α-LA group and ALLN＋ α-LA group was lower than in control group （ P 〈 0.05 for all）. Other indicators were ameliorated to some extent after intervention （ P 〈 0. 05 ）. Conclusion Both calpain inhibitor andα-lipoic acid can ameliorate cancer cachexia, and the combined use of them exerts a synerget- ic effect.

关 键 词：癌症恶病质 钙蛋白酶抑制剂 Α-硫辛酸 治疗 

分 类 号：R730.5[医药卫生—肿瘤]