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OA北大核心CSTPCD

Objective 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 di-vided 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 600 μg/(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.Quantita-tive 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 quan-titative reverse transcription PCR(RT-qPCR)showed that,compared with the NC group,the protein contents of collagenⅠ(col-Ⅰ),col-Ⅲcol-Ⅳand the relative mRNA expression of collagen type I alpha 1(COL1A1),COL3A1,COL4A1 and the protein levels of matrix metalloproteinase 2(MMP-2),MMP-9 significantly increased in the quadriceps femoris muscle of mice in HF group,while the protein content of adiponectin(APN)in quadriceps femoris muscle tissue(P＜0.001)and the relative expression of APN mRNA in visceral adipose(P＜0.001)significantly decreased.However,compared with HF group,the protein contents of col-Ⅰ,col-Ⅲ,col-Ⅳ,MMP-2,MMP-9 and the mRNA expressions of COL1A1,COL3A1,COL4A1 in the quadriceps femoris muscle of mice in HFL group significantly decreased.APN protein level in quadriceps femoris muscle(P＜0.001)and APN mRNA relative expression level in visceral adipose(P＜0.001)significantly increased.Conclusion Liraglutide can reduce skeletal muscle fibrosis induced by high-fat diet,and increase skeletal mus-cle mass and strength.The mechanism of liraglutide against skeletal muscle fibrosis may be related to the up-regulation of APN level and the inhibition of MMP-2 and MMP-9 expression in skeletal muscle.