利拉鲁肽可改善高脂诱导的小鼠骨骼肌纤维化和脂联素下调  

Effect of liraglutide on high-fat induced skeletal muscle fibrosis and adiponectin downregulation

作　　者：傅饶 吴永鑫 余靖 代昕 吴尧璇 李沅芬 吴江豪 张莹宵 肖谦[2] FU Rao;WU Yong-xin;YU Jing;DAI Xin;WU Yao-xuan;LI Yuan-fen;WU Jiang-hao;ZHANG Ying-xiao;XIAO Qian(The First Clinical College of Chongqing Medical University,Chongqing 400010,China;Department of Geriatrics,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China;The Fifth Clinical College of Chongqing Medical University,Chongqing 402160,China)

机构地区：[1]重庆医科大学第一临床学院老年医学,重庆400010 [2]重庆医科大学附属第一医院老年病科,重庆400010 [3]重庆医科大学第一临床学院全科医学,重庆400010 [4]重庆医科大学第五临床学院全科医学,重庆402160

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2024年第1期41-49,共9页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家博士后科学基金(2022TQ0398);重庆医科大学附属第一医院基金项目(PYJJ2022-01)。

摘　　要：目的探讨利拉鲁肽改善高脂饮食诱导的小鼠骨骼肌纤维化的作用,并进一步阐述可能的作用机制。方法30只6周龄C57BL/6雄性小鼠,随机分成3组(10只/组):普通饮食对照组(NC组)以普通饮食饲养,高脂饮食组(HF组)和高脂饮食加利拉鲁肽干预组(HFL组)以高脂饮食饲养,至14周龄(14周)。自15周龄起HFL组腹腔注射利拉鲁肽600μg/(kg·d),另2组给予等体积生理盐水,连续干预至30周龄(30周)。利用相对抓力(绝对抓力/体质量)评价小鼠肌肉力量。用双能X射线吸收法测量小鼠体质量和后肢质量,计算相对瘦质量及相对脂肪质量。实验结束时,用Western blot法检测股四头肌组织蛋白表达。实时定量逆转录PCR法检测组织中相关基因表达。结果在30周末时,与NC组相比,HF组小鼠体质量增加,而全身相对瘦质量和后肢相对瘦质量下降,后肢相对脂肪质量显著增加(P<0.001);与HF组相比,HFL组小鼠体质量减轻(P<0.001),全身相对瘦质量和后肢相对瘦质量有所升高,同时后肢相对脂肪质量降低,但差异无统计学意义(P>0.05)。14周末时,HF组和HFL组小鼠的相对抓力较NC组均有显著下降(P<0.001);30周末时HF组小鼠相对抓力较NC组进一步下降,而HFL组较HF组有显著升高(P<0.001)。Western blot和定量逆转录PCR结果显示,与NC组相比,HF组小鼠股四头肌组织中Ⅰ型胶原蛋白(collagenⅠ,col-Ⅰ)、col-Ⅲ、col-Ⅳ蛋白含量、α1-Ⅰ型胶原(collagen typeⅠalpha 1,COL1A1)、COL3A1、COL4A1 mRNA相对表达量和基质金属蛋白酶2(matrix metalloproteinase 2,MMP-2)和MMP-9蛋白量显著升高,股四头肌组织中脂联素(adiponectin,APN)蛋白含量(P<0.001)和内脏脂肪中APN mRNA相对表达量(P<0.001)显著下降;而HFL组则可逆转上述变化,与HF组相比,HFL组小鼠股四头肌组织中col-Ⅰ、col-Ⅲ、col-Ⅳ蛋白相对表达量、COL1A1、COL3A1、COL4A1 mRNA表达和MMP-2、MMP-9蛋白量显著降低,股四头肌组织中APN蛋白量(P<0.001Objective To explore the effect of liraglutide on skeletal muscle fibrosis induced by high-fat diet in mice,and elucidate its possible mechanism of action.Methods Thirty 6-week-old C57BL/6 male mice were randomly divided into three groups(10 mice/group):the control group(NC group)was fed with a regular diet,the high-fat diet group(HF group)and the high-fat diet intervention group(HFL group)were fed with a high-fat diet,until 14 weeks of age(14 week).From the age of 15 weeks,the HFL group received intraperitoneal injection of 600μg/(kg·d)of liraglutide,while the other two groups were given an equal volume of physiological saline for continuous intervention until the age of 30 weeks(30 week).Relative grip(absolute grip/body weight)was used to evaluate mouse muscle strength.Dualenergy X-ray absorption assay was used to scan the body and hind limb,to calculate the relative lean mass and relative fat mass.At the end of the experiment,Western blot was used to detect protein expression in the quadriceps femoris muscle tissue.Quantitative reverse transcription PCR was used to detect the expression of related genes in tissues.Results At the end of 30 weeks,compared with the NC group,the mice in the HF group gained weight,while the relative lean mass of the whole body and hind limbs decreased,and the relative fat mass of the hind limbs significantly increased(P<0.001).Compared with the HF group,the HFL group mice showed weight loss(P<0.001),increased relative lean mass of the whole body and hind limbs,and decreased relative fat mass of the hind limbs,but without statistical difference(P>0.05).At the end of the 14 week,the relative grip of the HF and HFL groups of mice decreased significantly compared to the NC group(P<0.001).At the end of 30 weeks,the relative grip of the HF group mice further decreased compared to the NC group,while the HFL group showed a significant increase compared to the HF group(P<0.001).Western blot and real-time quantitative reverse transcription PCR(RT-qPCR)showed that,compared with the NC group

关 键 词：利拉鲁肽 骨骼肌纤维化 脂联素 基质金属蛋白酶 

分 类 号：R685.5[医药卫生—骨科学]