榄香烯对肿瘤恶病质小鼠细胞因子TNF-ɑ IL-6和骨骼肌UPP信号通路的调节作用  

The effects of elemene on TNF-α,IL-6 and UPP signaling pathway in skeletal muscle of mice with cancer cachexia

作　　者：尹爱凝 李宏林 姚娓[1,2] Aining Yin;Honglin Li;Wei Yao(Department of Traditional Chinese Medicine,Second Hospital of Dalian Medical University,Dalian 116023,China;Institute of Integrative Medicine,Dalian Medical University,Dalian 116044,China)

机构地区：[1]大连医科大学附属第二医院中医科,辽宁省大连市116023 [2]大连医科大学中西医结合研究院/学院

出　　处：《中国肿瘤临床》2021年第9期440-445,共6页Chinese Journal of Clinical Oncology

基　　金：辽宁省高等学校基本科研项目(编号:LQ2017032)资助。

摘　　要：目的:研究通过建立肿瘤恶病质小鼠模型,研究榄香烯对肿瘤恶病质骨骼肌萎缩的缓解作用及其可能的机制。方法:C57BL/6小鼠皮下注射Lewis肺腺癌肿瘤细胞建立肿瘤恶病质模型。随机分为健康组、恶病质模型组、醋酸甲地孕酮组和榄香烯组。榄香烯口服乳等治疗14 d后,测量小鼠每日饮食量、肿瘤重量、去瘤体重、腓肠肌和胫骨前肌重量、肝脏重量,H&E染色检测腓肠肌肌丝横截面积,ELISA法检测血清IL-6和TNF-α水平,Western Blot检测腓肠肌中MAFBx、MURF-1的蛋白表达水平。结果:榄香烯组小鼠饮食量、去瘤体重及腓肠肌加胫骨前肌总重量较恶病质模型组增加,腓肠肌横截面积较恶病质模型组面积增大,IL-6及TNF-α水平较恶病质模型组明显下降,MAFBx、MURF-1的蛋白表达水平明显低于恶病质模型组(P<0.05)。同时,相对于醋酸甲地孕酮组,榄香烯组小鼠腓肠肌横截面积增大,IL-6及TNF-α水平降低,MAFBx、MURF-1的蛋白表达受到抑制(P<0.05)。结论:榄香烯可减轻肿瘤恶病质的骨骼肌萎缩,其机制可能与减少小鼠的能量消耗、降低血清TNF-α和IL-6水平、降低骨骼肌MAFBx、MURF-1的蛋白表达水平、调节UPP信号通路的活性有关。Objective: In this study, we established a mouse model of cancer cachexia to explore the underlying mechanisms, and the skeletal muscle atrophy alleviating effects of elemene. Methods: 40 mice were randomly assigned into the following groups: a healthy group;a cachexia model group;a megestrol acetate-treated group;an elemene-treated group. Lewis lung cancer cells were injected subcutaneously to create a cancer cachexia model. After 14 days of elemene oral milk treatment, daily food intake, tumor weight, tumor-free weight, gastrocnemius and tibialis anterior muscle mass, and liver mass were measured, the cross-sectional area of the gastrocnemius muscle was detected by H&E staining, IL-6 and TNF-ɑ serum levels were evaluated by ELISA, and the expression of MAFBx and MURF-1 proteins in gastrocnemius muscle was monitored by Western blot. Results: Compared with those in the cachexia model group, the daily food intake, tumor-free weight, and gastrocnemius and tibialis anterior muscle mass were increased in the elemene group. The cross-sectional area of the gastrocnemius muscle was increased, serum IL-6 and TNF-α levels were significantly decreased,and expression levels of MAFBx and MURF-1 proteins declined significantly(P<0.05). Compared with that in the megestrol-acetatetreated group, the cross-sectional area of the gastrocnemius muscle was increased in the elemene-treated group, and serum IL-6 and TNF-ɑ levels and MAFBx and MURF-1 protein expression levels were reduced(P<0.05). Conclusions: Elemene alleviates skeletal muscle atrophy in cancer cachexia, potentially by decreasing energy consumption, lowering serum TNF-α and IL-6 levels, attenuating MAFBx and MURF-1 protein expression in the skeletal muscle, and regulating the activity of the ubiquitin proteasome pathway(UPP) in mouse skeletal muscle.

关 键 词：肿瘤恶病质 榄香烯 骨骼肌消耗 细胞因子 泛素-蛋白酶体信号通路 

分 类 号：R965[医药卫生—药理学]