【摘要】 目的:研究钙蛋白酶抑制剂ALLN(N-acetyl-Leu-Leu-Norleucinal)对癌性恶病质小鼠的治疗作用。方法:将24只小鼠随机分成三组,即A组(健康对照组)、B组(荷瘤对照组)和C组(荷瘤+钙蛋白酶抑制剂治疗组),每组8只。将小鼠结肠腺癌Colon26(C26)细胞接种于B、C组小鼠右前腋窝皮下,建立恶病质模型后,C组小鼠用钙蛋白酶抑制剂ALLN干预7 d。每天监测小鼠体质量、摄食量、肿瘤体积。干预结束后,处死小鼠,检测去瘤体质量、腓肠肌和附睾脂肪湿重、血生化和细胞因子水平、骨骼肌中Calpain-1和泛素mRNA的表达。结果:与A组小鼠比,B组小鼠终末体质量、去瘤体质量、右后腓肠肌和双侧附睾脂肪湿重、血清总蛋白(TP)、清蛋白(ALB)和血糖(Glu)明显下降(P<0.01);三酰甘油(TG)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和C-反应蛋白(CRP)明显升高(P<0.01);肌肉组织中钙激活蛋白酶-1(Calpain-1)和泛素mRNA表达升高(P<0.01)。C组与B组比,血糖差异无统计学意义(P>0.05),其他各指标均有不同程度的改善。结论:钙蛋白酶抑制剂可能是通过抑制钙蛋白酶,减少肌肉蛋白消耗,从而改善癌性恶病质。更多还原

【Abstract】 Objective:To investigate the treatment effects of Calpain inhibitor ALLN(N-acetylleu-leu-norleucinal)on mouse model of cancer cachexia.Methods:Male Balb/c mice were randomly divided into three groups:A(healthy group),B(treated with cancer cells + DMSO),C(treated with cancer cells + DMSO + ALLN).The B and C groups were subcutaneously inoculated cancer cells Colon26(C26).The cancer cachexia model was successfully established and different groups were treated differently for 7 days.Body weight,food intake and tumor volume were measured everyday.Tumor-free body weight,wet weight of gastrocnemius muscle and epididymis adipose,serum levels of nutritional markers and cytokines,expression of nuclear factor-κB(NF-κB)and genes Calpain-1 and Ubiquitin were valuated after interventions.Results:The body weight,carcass weight,right rear side gastrocnemius muscle weight and epididymis wet weight in both sides of group B were respectively and significantly decreased(P <0.01)compared with group A.The serum levels of total protein(TP),albumin(ALB)and blood glucose(Glu)in B group were decreased evidently(P<0.01),levels of TG,TNF-α,IL-6,and CRP in B group were increased compared with group A(P<0.01),and levels of Calpain-1 and Ubiquitin mRNA in muscular tissue increased(P<0.01)in group B.The difference of blood glucose level between group B and group C had no statistic significance(P > 0.05),and the other indexes had improvement in group C.Conclusion:Calpain may have the potential to moderate cancer cachexia state in experimental mice through restraining calcium protease and reducing muscle protein consumption.更多还原