论文部分内容阅读
目的探讨蛋白酶体抑制剂MG132对肿瘤恶病质的作用及其可能的分子机制。方法经小鼠腋窝皮下注射结肠腺癌C26细胞,建立肿瘤恶病质模型,并设正常对照组(HC组)。将模型小鼠分为肿瘤恶病质组(CC组)和MG132治疗组(MG组),待小鼠进入恶病质状态后,CC组小鼠经腹腔注射0.1 ml生理盐水,MG组小鼠经腹腔注射0.1 mg/kg的MG132,7 d后处死小鼠,称量小鼠肿瘤、左侧腓肠肌和附睾脂肪的重量,测量腓肠肌纤维横切面积,ELISA法检测血清中炎性因子TNF-α和IL-6的水平,RT-PCR及Western blot法检测腓肠肌中IKBa、P65、MuRF1和MAFbx基因mRNA的转录水平及蛋白的表达水平。结果与CC组相比,MG组小鼠腓肠肌和附睾脂肪组织的重量分别增加了31.6%和39.5%(P<0.05),腓肠肌纤维横切面积增加了36.1%(P<0.05);血清中TNF-α和IL-6的水平分别降低了20.9%和42.0%(P<0.05);腓肠肌组织IKBa基因mRNA的转录水平和蛋白表达水平分别升高了132.7%和56.5%(P<0.05),MuRF1基因mRNA的转录水平和蛋白表达水平分别降低了70.1%和42.6%(P<0.05),MAFbx基因mRNA的转录水平和蛋白表达水平分别降低了76.8%和47.3%(P<0.05),P65基因mRNA的转录水平和蛋白表达水平分别降低了59.1%和53.1%(P<0.05)。结论 MG132改善肿瘤恶病质的分子机制可能与抑制NF-κB途径及MuRF1和MAFbx的表达、抑制炎症反应及肿瘤生长有关。
Objective To investigate the effect of proteasome inhibitor MG132 on tumor cachexia and its possible molecular mechanism. Methods C26 cells of colon adenocarcinoma were subcutaneously injected into the armpit of mice to establish a model of tumor cachexia, and a normal control group (HC group) was established. The model mice were divided into the tumor cachexia group (CC group) and the MG132 treatment group (MG group). After the mice entered the state of cachexia, the mice in the CC group were injected with 0.1 ml normal saline intraperitoneally, and the mice in the MG group were injected with 0.1 mg / kg of MG132. The mice were sacrificed on the 7th and 7th day. The weight of tumor, left gastrocnemius and epididymal fat were weighed, and the transverse area of gastrocnemius fiber was measured. The levels of TNF-α and IL-6 The mRNA and protein expression of IKBa, P65, MuRF1 and MAFbx in gastrocnemius muscle were detected by RT-PCR and Western blot. Results Compared with CC group, the weight of gastrocnemius muscle and epididymal adipose tissue of mice in MG group increased by 31.6% and 39.5% (P <0.05), and the cross-sectional area of gastrocnemius muscle fiber increased by 36.1% (P <0.05) (P <0.05). The mRNA and protein expression of IKBa mRNA in gastrocnemius muscle increased by 132.7% and 56.5%, respectively (P <0.05), while MuRF1 and IL-6 decreased by 20.9% and 42.0% (P <0.05). The mRNA and protein expression levels of MAFbx decreased by 76.8% and 47.3% (P <0.05), respectively. The mRNA and protein expression levels of P65 mRNA and protein were decreased by 70.1% and 42.6% The transcriptional level and protein expression level decreased by 59.1% and 53.1%, respectively (P <0.05). Conclusion The molecular mechanism of MG132 in improving cachexia may be related to the inhibition of NF-κB pathway, the expression of MuRF1 and MAFbx, the inhibition of inflammatory reaction and tumor growth.