摘要
目的研究玉米低聚肽(corn oligopeptide,COP)对地塞米松诱导的肌肉萎缩的改善作用。方法49只8周龄Sprague-Dawley雄性大鼠分为空白组(10只)和模型组(39只),模型组腹腔注射地塞米松(1.0 mg/kg),空白组注射生理盐水。19 d后,空白组取1只、模型组取3只观察模型是否构建成功。造模成功后,将模型组随机分为模型对照组、COP低剂量组(COP-L组,0.5 g/kg)、COP中剂量组(COP-M组,1.0 g/kg)和COP高剂量组(COP-H组,2.0 g/kg),9只/组,干预33 d后测大鼠抓力,随后麻醉处死,分离腓肠肌、比目鱼肌、胫骨前肌和跖肌称重,并测肌纤维直径、Atrogin-1和MuRF-1 mRNA相对表达量及腓肠肌非靶向代谢组学。结果与空白组相比,模型组大鼠体重显著降低(P<0.05),肌原纤维破裂,提示造模成功。与模型对照组相比,COP-L组、COP-M组抓力提高(P<0.05);COP-L组、COP-H组腓肠肌、比目鱼肌肌肉系数增大(P<0.05),COP-L组、COP-M组跖肌肌肉系数增大(P<0.05);COP 3个剂量组大鼠胫骨前肌肌纤维直径增加(P<0.05),COP-M组、COP-H组跖肌肌纤维直径增加(P<0.05);COP 3个剂量组比目鱼肌Atrogin-1 mRNA相对表达量均下降(P<0.05),COP-L组、COP-H组MuRF-1 mRNA相对表达量下降(P<0.05)。腓肠肌中氨基酸合成通路、糖酵解通路、酸代谢通路激活。结论给予COP可显著改善地塞米松诱导的肌肉萎缩,其机制可能与COP减小泛素-蛋白酶体途径中关键基因Atrogin-1、MuRF-1表达和增加肌肉中重要氨基酸的生物合成有关。
Objective To explore the effect of corn oligopeptide(COP)on dexamethasone-induced muscle atrophy.Methods Forty-nine male Sprague-Dawley rats aged 8 weeks were divided into blank group(n=10)and model group(n=39).The rats in the model group were intraperitoneally injected with dexamethasone(1.0 mg/kg),and the rats in the blank group were injected with normal saline.After 19 days,one rat in the blank group and three rats in the model group were taken to observe whether the model was successfully constructed.After successful modeling,the rats in the model group were randomly divided into model control group,COP low-dose group(COP-L group,0.5 g/kg),COP medium-dose group(COP-M group,1.0 g/kg)and COP high-dose group(COP-H group,2.0 g/kg),with 9 rats in each group.After 33 days,the grip strength of the rats was measured,and then the gastrocnemius,soleus,tibialis anterior and metatarsal muscles were separated and weighed,and muscle fiber diameter,relative expression of Atrogin-1 and MuRF-1 mRNA were measured.Non-targeted metabolomics of gastrocnemius muscle were measured.Results Compared with that in the blank group,the body weight of rats in the model group reduced(P<0.05),and myofibril rupture was observed,indicating that the model was successful.Compared with those in the model control group,the grip strength increased in the COP-L and COP-M groups(P<0.05);the muscle coefficients of gastrocnemius and soleus in the COP-L and COP-H groups increased(P<0.05),and the muscle coefficients of plantaris in the COP-L and COP-M groups increased(P<0.05);the muscle fiber diameter of the tibial anterior muscle increased in the three doses of COP groups(P<0.05),and the muscle fiber diameter of the plantaris muscle increased in the COP-M and COP-H groups(P<0.05);the relative expression of Atrogin-1 mRNA decreased in the three doses of COP groups(P<0.05),while the relative expression of MurF-1 mRNA in the COP-L and COP-H groups decreased(P<0.05).The amino acid synthesis pathway,glycolysis pathway,and acid metabolism pathway were activated in gastrocnemius muscle.Conclusionss COP can significantly improve the muscle atrophy induced by dexamethasone.The mechanism may be related to the decrease of Atrogin-1 and MuRF-1 expression in ubiquitin-proteasome pathway and the increase of amino acid biosynthesis.
作者
汪云凤
闫九明
周正明
郭鉴葵
魏瑶瑶
景小凡
廖欣怡
胡雯
WANG Yunfeng;YAN Jiuming;ZHOU Zhengming;GUO Jiankui;WEI Yaoyao;JING Xiaofan;LIAO Xinyi;HU Wen(West China School of Public Health/West China Fourth Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China;Department of Clinical Nutrition,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China)
出处
《华西医学》
CAS
2023年第3期429-437,共9页
West China Medical Journal
基金
国家重点研发计划(2016YFD0400604)。