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目的 研究核因子 (NF) κB和促炎细胞因子在癌性恶病质形成中的作用以及吲哚美辛(IND)对其调控作用。方法 30只雄性BALB/c小鼠随机分为 5组 :A组为对照组 ,B组为荷瘤加生理盐水组 ,C组为荷瘤加IND(0 2 5mg/kg)组 ,D组为荷瘤加IND (0 5mg/kg)组 ;E组为荷瘤加IND(2 0mg/kg)组。利用鼠结肠腺癌 2 6细胞株皮下接种诱导癌性恶病质。恶病质出现后 ,皮下分别给予生理盐水以及不同剂量IND。 1周后检测动物血清肿瘤坏死因子 α(TNF α)和白细胞介素 (IL 6 )浓度和脾脏中NF κB活性。整个实验过程中跟踪监测动物体重以及腓肠肌重量改变。结果所有接种动物均出现恶病质 ,食物摄入量组间无明显差异。第 16天B组体重为A组的 82 0 % (P <0 0 1) ,腓肠肌重量下降了 2 8 7% (P <0 0 1) ,血清TNF α和IL 6浓度显著升高 (P <0 0 1)。 0 5mg/kg的IND腓肠肌重量显著增加 (P <0 0 1) ,血清TNF α(P <0 0 5 )和IL 6水平降低 (P <0 0 1)。凝胶电泳迁移率分析显示B组小鼠脾脏NF κB活性较A组显著增加 (P <0 0 1) ,IND降低NF κB活性 ,在 0 5mg/kg剂量组最为显著 (P <0 0 1)。且脾脏NF κB活性与细胞因子浓度呈正线性相关(rTNF α=0 918,PTNF α=0 0 2 8;rIL 6=0 884 ,PIL 6=0 0 4 6 )。结论 癌性恶病质?
Objective To investigate the role of nuclear factor (NF) κB and pro-inflammatory cytokines in the carcinogenesis of cancerous cachexia and the role of indomethacin (IND) in its regulation. Methods Thirty male BALB / c mice were randomly divided into 5 groups: group A as control group, group B as tumor bearing plus saline group, group C as tumor bearing plus IND (0 2 5mg / kg) group, group D as Tumor plus IND (0 5mg / kg) group; E group with tumor plus IND (20mg / kg) group. Subcutaneous inoculation of murine colon adenocarcinoma cell line 26 induced malignant cachexia. After the occurrence of cachexia, subcutaneous saline and different doses were given IND. One week later, the concentrations of tumor necrosis factor α (TNF α) and interleukin (IL 6) in serum and NF κB activity in spleens were detected. During the whole experiment, the weight of animals and gastrocnemius muscle weight were tracked and monitored. Results All vaccinated animals showed cachexia with no significant difference in food intake. On the 16th day, the body weight of group B was 82.0% (P <0.01) in group A, and the weight of gastrocnemius muscle was decreased by 28.7% (P <0.01), while the levels of TNFα and IL 6 in serum in group B were significantly increased (P < 0 0 1). The weight of IND gastrocnemius at 5 mg / kg significantly increased (P <0.01), and the levels of serum TNFα (P <0 05) and IL 6 decreased (P <0.01). Gel electrophoretic mobility shift assay showed that NF-κB activity in spleens of B group was significantly higher than that of A group (P <0.01), while IND decreased NF κB activity (P 0 01) . NF-κB activity in spleen was positively correlated with cytokine concentration (rTNF α = 0 918, PTNF α = 0 0 2 8; rIL 6 = 0 884, PIL 6 = 0 0 4 6). Conclusion Cancer cachexia?