摘要
Abstract
Objective To explore the effects of glucagon-like peptide-2(GLP-2)on hindlimb suspension-induced skel-etal muscle atrophy in mice.Methods A total of 18 8-week-old male C57BL/6 mice were randomly divided into three groups:control group,hindlimb suspension group(HLS group)and intervention group(HLS+GLP-2 group),with 6 mice in each group.Mice in the HLS+GLP2 group received daily subcutaneous injections of GLP-2(300 μg·kg-1·d-1),while mice in the control group and HLS group were administered an equivalent volume of 1％DMSO solvent.The samples of skele-tal muscles were harvested for analysis after 4 weeks of intervention.Muscle weight and grip strength were measured.HE stai-ning and muscle fiber cross-sectional area(CSA)were used to assess atrophy.qRT-PCR and Western blot analyzed expression of muscle metabolism markers and phosphorylation levels of key regulatory signaling pathways.Results After 4 weeks,body weight increased in all groups without statistical significance(P＞0.05).Compared with the control group,the HLS group showed significant reduction in weights of quadriceps(QD),tibialis anterior(TA),gastrocnemius(GA)and soleus(SOL)(P＜0.05);compared with the HLS group,the weights of GA and SOL in the HLS+GLP-2 group increased(P＜0.05).Compared with the control group,the muscle strength in the HLS group decreased(P＜0.01);compared with the HLS group,the muscle strength in the HLS+GLP-2 group improved(P＜0.05).Compared with the control group,the morphology of GA fibers in the HLS group atrophied and the cross-sectional area of muscle fibers decreased(P＜0.001);the muscle atrophy in the HLS+GLP2 group was improved compared with the HLS group,and the cross-sectional area of muscle fibers increased(P＜0.05).The Western blot results showed that compared with the control group,the expressions of muscle-specific ring fin-ger protein 1(MuRF-1)and muscle atrophy Fbox protein(atrogin-1)in GA in the HLS group increased(P＜0.05),and the protein expressions of myogenic regulatory factor(MyoD)and myosonietin(MyoG)decreased(P＜0.05).Compared with the HLS group,the protein expressions of MuRF-1 and Atrogin-1 in GA in the HLS+GLP-2 group decreased(P＜0.05),while the protein expressions of MyoD(P＜0.01)and MyoG(P＜0.05)increased.Compared with the control group,the phosphorylation level of protein kinase B(AKT)in GA in the HLS group decreased(P＜0.05);compared with the HLS group,the phosphorylation level of AKT in GA in the HLS+GLP-2 group increased(P＜0.05).Conclusion GLP-2 im-proves HLS-induced skeletal muscle atrophy in mice,and this regulation may be related to AKT phosphorylation.关键词
肌少症/骨骼肌/废用性肌萎缩/胰高血糖素样肽-2/蛋白激酶BKey words
sarcopenia/skeletal muscle/disuse muscular atrophy/glucagon-like peptide-2/protein kinase B
