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机构地区:[1]福建医科大学附属第一医院胃肠外科,福建福州350005
出 处:《肠外与肠内营养》2013年第5期295-298,共4页Parenteral & Enteral Nutrition
基 金:国家自然科学基金资助(81272465)
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。Objective: To investigate the treatment effects of Calpain inhibitor ALLN (N-acetyl- leu-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 differ- ently 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-KB (NF-KB) and genes Calpain-1 and Ubiquitin were valua- ted 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-c~, 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 experimen- tal mice through restraining calcium protease and reducing muscle protein consumption.
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