多西他赛在癌症化疗的小鼠模型中不会损害骨骼肌力量的产生。

Docetaxel does not impair skeletal muscle force production in a murine model of cancer chemotherapy.

作者信息

Chaillou Thomas, McPeek Ashley, Lanner Johanna T

机构信息

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

School of Health Sciences, Örebro University, Örebro, Sweden.

出版信息

Physiol Rep. 2017 Jun;5(11). doi: 10.14814/phy2.13261.

Abstract

Chemotherapy drugs such as docetaxel are commonly used to treat cancer. Cancer patients treated with chemotherapy experience decreased physical fitness, muscle weakness and fatigue. To date, it is unclear whether these symptoms result only from cancer-derived factors or from the combination of cancer disease and cancer treatments, such as chemotherapy. In this study, we aimed at determining the impact of chemotherapy on force production of hind limb muscles from healthy mice treated with docetaxel. We hypothesized that docetaxel will decrease maximal force, exacerbate the force decline during repeated contractions and impair recovery after fatiguing stimulations. We examined the function of soleus and extensor digitorum longus (EDL) muscles 24 h and 72 h after a single injection of docetaxel (acute treatment), and 7 days after the third weekly injection of docetaxel (repeated treatment). Docetaxel was administrated by intravenous injection (20 mg/kg) in female FVB/NRj mice and control mice were injected with saline solution. Our results show that neither acute nor repeated docetaxel treatment significantly alters force production during maximal contractions, repeated contractions or recovery. Only a tendency to decreased peak specific force was observed in soleus muscles 24 h after a single injection of docetaxel (-17%, =0.13). In conclusion, docetaxel administered intravenously does not impair force production in hind limb muscles from healthy mice. It remains to be clarified whether docetaxel, or other chemotherapy drugs, affect muscle function in subjects with cancer and whether the side effects associated with chemotherapy (neurotoxicity, central fatigue, decreased physical activity, etc.) are responsible for the experienced muscle weakness and fatigue.

摘要

多西他赛等化疗药物常用于治疗癌症。接受化疗的癌症患者会出现体能下降、肌肉无力和疲劳等症状。迄今为止,尚不清楚这些症状仅仅是由癌症衍生因素导致的,还是由癌症疾病与化疗等癌症治疗手段共同作用引起的。在本研究中,我们旨在确定化疗对用多西他赛治疗的健康小鼠后肢肌肉力量产生的影响。我们假设多西他赛会降低最大力量,加剧重复收缩过程中的力量下降,并损害疲劳刺激后的恢复能力。我们在单次注射多西他赛(急性治疗)后24小时和72小时,以及在每周第三次注射多西他赛(重复治疗)后7天,检查了比目鱼肌和趾长伸肌(EDL)的功能。通过静脉注射(20毫克/千克)将多西他赛给予雌性FVB/NRj小鼠,对照组小鼠注射生理盐水溶液。我们的结果表明,无论是急性还是重复多西他赛治疗,在最大收缩、重复收缩或恢复过程中,均未显著改变力量产生。单次注射多西他赛后24小时,仅在比目鱼肌中观察到峰值比肌力有下降趋势(-17%,P=0.13)。总之,静脉注射多西他赛不会损害健康小鼠后肢肌肉的力量产生。多西他赛或其他化疗药物是否会影响癌症患者的肌肉功能,以及与化疗相关的副作用(神经毒性、中枢性疲劳、身体活动减少等)是否导致了所经历的肌肉无力和疲劳,仍有待阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbe1/5471428/b66dc88a8a39/PHY2-5-e13261-g001.jpg

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