| 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 |
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| 引用本文： | 尹爱凝,李宏林,姚娓.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[J].中国肿瘤临床,2021,48(9):440-445. |
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| 作者姓名： | 尹爱凝 李宏林 姚娓 |
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| 作者单位： | ①.大连医科大学附属第二医院中医科（辽宁省大连市116023） |
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| 基金项目： | 辽宁省高等学校基本科研项目LQ2017032 |
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| 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。
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| 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 |
| 收稿时间： | 2021-01-13 |
The effects of elemene on TNF-α, IL-6 and UPP signaling pathway in skeletal muscle of mice with cancer cachexia |
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| Affiliation: | ①.Department of Traditional Chinese Medicine, Second Hospital of Dalian Medical University, Dalian 116023, China②.Institute of Integrative Medicine, Dalian Medical University, Dalian 116044, China |
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| Abstract: | 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-ɑ levels were significantly decreased, and expression levels of MAFBx and MURF-1 proteins declined significantly (P < 0.05). Compared with that in the megestrol-acetate? treated 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. |
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