钙蛋白酶抑制剂治疗癌性恶病质小鼠的实验研究

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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 study the therapeutic effect of calpain inhibitor ALLN (N-acetyl-Leu-Leu-Norleucinal) on cancerous cachexia mice. Methods: Twenty-four mice were randomly divided into three groups: group A (healthy control group), group B (tumor-bearing control group) and group C (tumor-bearing plus calpain inhibitor treatment group), with 8 mice in each group. The mouse colon adenocarcinoma Colon26 (C26) cells were inoculated subcutaneouly in the anterior armpit of mice in groups B and C to establish a rat model of cachexia. Rats in group C were treated with the calpain inhibitor ALLN for 7 days. Mice were monitored daily for body weight, food intake and tumor volume. At the end of the intervention, the mice were sacrificed and the tumor mass, gastrocnemius and epididymal fat wet weight, blood biochemical and cytokine levels, and expression of Calpain-1 and ubiquitin mRNA in skeletal muscle were measured. RESULTS: Compared with group A, the body weight, tumor volume, weight of wet tine of right hind gastrocnemius and epididymal fat, serum total protein (TP), albumin (ALB) and blood glucose (P <0.01). The levels of triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) <0.01). The expressions of Calpain-1 and Ubiquitin mRNA in muscle tissue were increased (P <0.01). There was no significant difference in blood glucose between C group and B group (P> 0.05), while other indexes all improved to some extent. Conclusion: Calpain inhibitors may improve cancerous cachexia by inhibiting calpain and decreasing muscle protein consumption.
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