巴戟天多糖调控线粒体自噬通路减轻小鼠骨骼肌萎缩的机制研究  

Study on Mechanism of Morinda Officinalis Polysaccharide Regulating Mitophagy Pathway to Reduce Skeletal Muscle Atrophy in Mice

作　　者：冯书娈 张小河 陈冬青 潘祖林 FENG Shuluan;ZHANG Xiaohe;CHEN Dongqing;PAN Zulin(Shijiazhuang People's Hospita,Shijiazhuang Hebei 050000,China)

机构地区：[1]石家庄市人民医院,河北石家庄050000

出　　处：《中医药导报》2022年第11期36-40,共5页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：石家庄市科学技术项目(181461293)。

摘　　要：目的:探讨巴戟天多糖调控线粒体自噬通路减轻小鼠骨骼肌萎缩的机制。方法:将60只C57BL/6小鼠随机分为对照组、模型组、巴戟天多糖低剂量组、巴戟天多糖中剂量组、巴戟天多糖高剂量组、巴戟天多糖高剂量+EX-527组,每组10只。除对照组外,其余各组小鼠通过尾部悬吊法建立小鼠骨骼肌萎缩模型。各给药组分别灌胃给予相应药物,对照组及模型组小鼠均给予等体积的生理盐水灌胃,1次/d,连续给药7 d。比较各组小鼠胫前肌与体质量的比值变化;分离胫前肌组织,观察各组小鼠肌纤维萎缩状况并比较胫前肌相对横截面积;检测各组小鼠胫前肌IL-18、IL-1β水平;透射电镜观察胫前肌中线粒体结构变化;Western blotting检测各组小鼠胫前肌SIRT1/叉头盒转录因子O3(FOXO3)/PTEN诱导性激酶蛋白1(PINK1)/E3泛素连接酶(Parkin)通路蛋白表达。结果:与对照组比较,模型组小鼠胫前肌与体质量比值、胫前肌相对横截面积以及胫前肌组织SIRT1、PINK1、FOXO3、Parkin蛋白相对表达量均明显降低(P<0.05),胫前肌组织IL-18、IL-1β含量均明显升高(P<0.05),骨骼肌线粒体数量减少,线粒体肿胀伴嵴结构消失;经不同剂量的巴戟天多糖干预后,线粒体自噬增强,胫前肌与体质量比值、胫前肌相对横截面积、SIRT1、PINK1、FOXO3、Parkin蛋白相对表达量均明显升高(P<0.05),胫前肌组织IL-18、IL-1β含量均明显降低(P<0.05);与巴戟天多糖高剂量组比较,加入EX-527后逆转了巴戟天多糖对骨骼肌萎缩小鼠的改善作用。结论:巴戟天多糖可以改善小鼠骨骼肌萎缩,可能与激活SIRT1/FOXO3/PINK1/Parkin通路介导的线粒体自噬有关。Objective: To investigate the mechanism of Morinda officinalis polysaccharide(MOP) in reducing skeletal muscle atrophy in mice by regulating mitophagy pathway. Methods: 60 C57BL/6 mice were randomly divided into control group, model group, MOP low, medium, and high dose groups, and MOP high dose + EX-527group, with 10 mice in each group. In addition to the control group, the skeletal muscle atrophy model of mice in other groups was established by tail suspension method. Each administration group was given corresponding drugs by gavage, and the control group and model group mice were given equal volume of normal saline by gavage once a day for 7 consecutive days. The changes of the ratio of tibialis anterior muscle to body mass were compared. The tissue of tibialis anterior muscle was isolated, and the atrophy of muscle fibers was observed and the relative cross-sectional area of tibialis anterior muscle was compared in each group. The levels of IL-18and IL-1β in tibialis anterior muscle of mice in each group were detected. The structure of mitochondria in tibialis anterior muscle was observed by transmission electron microscope. The expression of SIRT1/forkhead box transcription factor O3(FOXO3)/PTEN induced kinase protein 1(PINK1)/E3 ubiquitin ligase(Parkin) pathway proteins in anterior tibial muscle of each group was measured by Western blotting. Results: Compared with the control group, the ratio of tibialis anterior muscle to body mass, the relative cross-sectional area of tibialis anterior muscle,the relative expressions of SIRT1, PINK1, FOXO3, and Parkin protein in tibialis anterior muscle tissue of mice in the model group were significantly decreased(P<0.05), the content of IL-18 and IL-1β in tibialis anterior muscle tissue were significantly increased(P<0.05), the number of skeletal muscle mitochondria was reduced, and the mitochondria were swelled with the disappearance of crista structure. After the intervention of MOP at different doses, the mitochondrial autophagy was enhanced, the ratio of tibialis

关 键 词：骨骼肌萎缩 巴戟天多糖 尾部悬吊 SIRT1/FOXO3/PINK1/Parkin信号通路 小鼠 

分 类 号：R285.5[医药卫生—中药学]