Caspase-3在小鼠肿瘤恶病质肌肉蛋白消耗中的作用

目的：探讨半胱氨酸天冬氨酸蛋白酶3（Caspase-3）在小鼠肿瘤恶病质状态下骨骼肌中的表达，阐明Caspase-3与细胞凋亡及肿瘤恶病质骨骼肌蛋白消耗的关系。方法：小鼠结肠腺癌Colon26（CT26）细胞接种BALB/c小鼠诱导肿瘤恶病质模型为肿瘤组，同时设对照组，每组24只。每天监测各组小鼠体质量，并分别在第8、14和20天各处死8只小鼠，检测小鼠左侧腓肠肌组织质量、纤维横切面积、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）水平和Caspase-3蛋白表达水平及腓肠肌细胞凋亡率。结果：第14天肿瘤组小鼠出现恶病质症状，去瘤体质量下降大于对照组小鼠体质量的20%(P<0.05)，小鼠进入肿瘤恶病质期。与同期对照组比较，随着接种细胞时间的延长，肿瘤组小鼠体质量、去瘤体质量、腓肠肌组织质量及纤维横切面积均减小（P<0.05），TNF-α、IL-6水平和Caspase-3蛋白表达水平及骨骼肌细胞凋亡率均显著升高（P<0.05）。Caspase-3蛋白表达水平与腓肠肌质量及横切面积呈负相关关系（r=－0.716,P<0.05;r=－0.694,P<0.05）,与TNF-α和IL-6水平呈正相关关系（r=0.742，P<0.05;r=0.675,P<0.05）。结论：Caspase-3可能是肿瘤恶病质促进骨骼肌组织蛋白消耗的关键性因子。

Effect of Caspase-3 in skeletal muscle protein consumption of cancer cachexia mice

Objective To explore the expression of caspase-3in skeletal muscle of the mice in the state of cancer,and to elucidate the relationship between Caspase-3and apoptosis,consumption of skeletal muscle protein in cancer cachexia.Methods 48male BALB/c mice were randomly divided into cancer cachexia group and control group(n=24).The mice in cancer cachexia group were inoculated with mouse colon 26adenocarcinoma cells.The body weights of the mice in two groups were detected daily.Eight mice in each group were executed to test the weight of left gastrocnemius,fiber crosscut area,the expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),Caspase-3proteins and the apoptotic rate of gastrocnemius cells on day 8,14,and 20,respectively.Results The mice in cancer cachexia group appeared cachectic symptoms on day 14,the non-tumor body weight was decreased more than 20%of that in control group(P<0.05).Compared with control group at the same time,the mouse body weight,non-tumor body weight,the weight of left gastrocnemius and the fiber crosscut area of the mice in cancer cachexia group were obviously decreased with the prolongation of inoculation time(P<0.05),whereas the expression levels of TNF-α,IL-6,Caspase-3proteins and the apoptotic rate of muscle cells were obviously increased after tumor inoculation(P<0.05).The level of Caspase-3protein was negatively correlated with the weight of gastrocnemius and fiber crosscut area(r=-0.716,P<0.05;r=-0.694,P<0.05),and the level of Caspase-3was positively correlated with the levels of TNF-αand IL-6(r=0.742,P<0.05;r=0.675,P<0.05).Conclusion Caspase-3may be a key factor in the protein comsumption of skeletal muscle in cancer cachexia.