核因子-κB在癌性恶病质形成中的作用

Role of NF-kappa B in cancer cachexia

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 assess the putative involvement of NF κB and pro inflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND) on cachexia. Methods Thirty young male BALB/c mice were divided randomly into five groups: A, control; B, tumor bearing plus saline; C, tumor bearing plus IND (0 25 mg/kg); D, tumor bearing plus IND (0 5 mg/kg); and E, tumor bearing plus IND (2 0 mg/kg). Colon 26 adenocarcinoma cells of murine were inoculated subcutaneously to induce cachexia. Saline and IND were given intraperitoneally daily for 7 days from the onset of cachexia to sacrifice. Food intake and body composition were documented, serum TNF α and IL 6 levels and activity of NF κB in spleen were investigated in all animals. Results Cachexia was observed in all tumor bearing mice. No difference was found between groups in food intake ( P >0 05). By day 16, body weights of non tumor mice were about 82 0% of healthy controls ( P <0 01), and the weight of gastrocnemius was decreased by 28 7% ( P <0 01) Gastrocnemius weight was increased markedly ( P <0 01) after treatment of IND (0 5 mg/kg). Tumor bearing caused a significant increase in serum TNF α and IL 6 levels ( P <0 01). The concentration of TNF α ( P <0 05) and IL 6 ( P <0 01) in tumor bearing mice was reduced after administration of 0 5 mg/kg IND for 7 days. NF κB activation in the spleen was increased in tumor bearing mice in comparison with controls. NF κB activity was reduced in mice treated with IND. The maximal inhibition was observed at an dosage of 0 5 mg/kg ( P <0 01). Liner positive correlation was found between NF κB activity and cytokine levels ( r TNF α =0 918, P TNF α =0 028; r IL 6 =0 884, P IL 6 =0 046). Conclusions Cachexia induced by colon 26 adenocarcinoma cells may be partially attributed to the enhanced TNF α and IL 6 levels which is controlled by NF κB. IND may inhibit the activation of NF κB, decrease serum TNF α and IL 6 levels and thus alleviate the cachexia.