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目的:探讨蛋白酶体抑制剂对恶病质小鼠炎症细胞因子的合成和调控作用。方法:采用C26结肠癌细胞接种小鼠皮下,诱导恶病质模型,每天监测小鼠体重、食物摄入量和肿瘤体积,于肿瘤接种后第6、9、12和15天,每天给予荷瘤鼠腹腔注射生理盐水和不同剂量的蛋白酶体抑制Bortezomib(0.1、0.5和1.0mg/kg),第16天处死小鼠,检测肿瘤组织NF-κB活性、IL-6以及血清IL-6和IL-10水平。结果:第16天时,生理盐水组出现显著的体重和去瘤体重的下降(P<0.01)、腓肠肌萎缩及附睾脂肪的降解(P<0.01),同时血清IL-6、IL-10和肿瘤组织IL-6水平显著升高(P<0.01)。Bortezomib不同程度地抑制了去瘤体重、腓肠肌和附睾脂肪的降解。Bortezomib剂量依赖性地抑制了肿瘤组织NF-κB的激活及IL-6的合成,以1.0mg/kg组最显著。0.5mg/kg组显著抑制了血清IL-6水平的升高(P<0.01)。0.5和1.0mg/kg组明显抑制肿瘤生长(P<0.01)。结论:蛋白酶体抑制剂通过抑制肿瘤组织NF-κB的激活,从而抑制癌性炎性反应和组织成分降解,改善恶病质。
Objective: To investigate the effects of proteasome inhibitor on the synthesis and regulation of inflammatory cytokines in cachexia mice. Methods: C26 colon cancer cells were used to inoculate mice subcutaneously to induce cachexia model. Body weight, food intake and tumor volume were monitored daily. On the 6th, 9th, 12th and 15th day after tumor inoculation, Bortezomib (0.1, 0.5 and 1.0 mg / kg) was injected into normal saline and different doses of proteasome. Mice were killed on the 16th day. The activity of NF-κB, IL-6 and the levels of IL-6 and IL-10 . Results: On the 16th day, the body weight of the saline group decreased significantly (P <0.01), the atrophy of the gastrocnemius muscle and the degradation of epididymal fat (P <0.01), while the levels of IL-6, IL-10 and tumor tissue IL-6 levels were significantly increased (P <0.01). Bortezomib to varying degrees inhibit tumor weight, gastrocnemius and epididymal fat degradation. Bortezomib dose-dependently inhibited the activation of NF-κB and the synthesis of IL-6 in the tumor tissue, most notably in the 1.0 mg / kg group. 0.5mg / kg group significantly inhibited the increase of serum IL-6 level (P <0.01). 0.5 and 1.0 mg / kg significantly inhibited tumor growth (P <0.01). Conclusion: Proteasome inhibitors can inhibit the inflammatory reaction and degradation of tissue components and improve cachexia by inhibiting the activation of NF-κB in tumor tissue.