短期间歇和急性低氧对大鼠快慢肌萎缩的影响及其作用机制

目的:探讨不同低氧干预模式对大鼠快肌和慢肌萎缩的影响差异及可能的分子机制.方法:24只10周龄雄性SD大鼠分为常氧对照组(C组)、短期间歇低氧组(IH组,于12.4％O2暴露8 h/d,持续4周)和急性低氧组(AH组,连续3 d暴露于12.4％O2),每组8只.干预后测定抓力,胫骨前肌(TA,快肌)和比目鱼肌(SOL,...

Effects of short-term intermittent and acute hypoxia on fast-and slowtwitch muscle atrophy in rats and its mechanism

AIM:To investigate the effects of different hypoxia intervention modes on fast-and slow-twitch muscle atrophy in rats and the possible molecular mechanism.METHODS:Twenty-four 10-week-old male SD rats were divided into normoxic control group(C group),short-term intermittent hypoxia group(IH group,exposed to 12. 4% oxygen for 8 h/d for 4 weeks)and acute hypoxia group(AH group,living in hypoxic room with 12. 4% oxygen for 3 d),with 8 rats in each group. After intervention,the holding power,wet weight of tibialis anterior muscle(TA,fast-twitch muscle)and soleus muscle(SOL,slow-twitch muscle),and muscle fiber cross-sectional area(FCSA)were tested. The content of puromycin(Puro)and ubiquitin(Ub)was measured by Western blot,and the protein accumulation(Puro/Ub)was calculated. Differentially expressed genes in IH/C group and AH/C group were screened by RNA sequencing. The enriched biological processes and pathways of these genes were analyzed. The expression of key differential genes was verified by RTqPCR.RESULTS:After intervention,the relative holding power in AH group was significantly lower than that in C group(P<0. 01). The relative wet weight of TA and SOL in AH group was higher than that in IH group(P<0. 05). The FCSA of TA and SOL in IH group and AH group were significantly lower than those in C group(P<0. 01). The protein accumulation of TA in IH group was significantly higher than that in C group,while that in AH group was significantly lower than that in IH group(P<0. 01). The protein accumulation of SOL in IH group was significantly lower than that in C group,while that in AH group was significantly higher than that in IH group(P<0. 01). The differential genes of TA in IH/C group were mainly up-regulated,and the differential genes of SOL in AH/C group were mainly up-regulated. In TA,the up-regulated genes in IH/C group were mainly enriched in antioxidant and glucose metabolism,and PPAR signaling pathway was involved. The up-regulated genes in AH/C group were mainly enriched in the transformation between fast-and slow-twitch muscle,oxidative stress,inflammation and cell death. In SOL,the up-regulated genes in IH/C group and AH/C group were mainly enriched in apoptosis,immune response and oxidative stress,and the TNF,TGF-β and JAK-STAT pathways were involved. The key differentially expressed genes verified by RT-qPCR were consistent with the results of sequencing.CONCLUSION:Short-term intermittent hypoxia exposure may resist atrophy by increasing the antioxidant capacity of fast-twitch muscle(TA)in rats,while acute hypoxia may promote the atrophy of fast-twitch muscle(TA)and slow-twitch muscle(SOL)by increasing the capacity of oxidative stress,inflammatory response and apoptosis in rats.