不同光照节律对内毒素血症大鼠的骨骼肌代谢的影响

The effects of light exposure on skeletal muscle wasting in rats with endotoxemia

目的持续光照可导致机体的高分解代谢。文章主要比较不同光照节律对内毒素血症大鼠骨骼肌代谢的影响,寻找最优化的能减少骨骼肌消耗和加速康复的光照节律。方法将54只SD大鼠随机数字表法分为3组:对照组(腹腔注射等渗盐水+12 h/12 h光照-黑暗循环7 d)、规律光照组(腹腔注射脂多糖+12 h/12 h光照-黑暗循环7 d)和持续光照组(腹腔注射脂多糖+持续光照7 d)。第8天时处死实验动物,并检测骨骼肌代谢产物3-甲基组氨酸(3-MH)和酪氨酸,萎缩基因MAFbx和MuRF-1 mRNA和下丘脑组织钟基因BMAL1、CLOCK和神经肽POMC的表达等指标。结果持续光照组的摄食量、体重增长比和趾长伸肌/体重比明显低于规律光照组(P<0.05),且两组均明显低于对照组(P<0.01)。持续光照组大鼠的骨骼肌代谢产物3-MH和酪氨酸[(6.200±0.273)和(461.039±13.292)nmol/g]相较于规律光照组[(5.197±0.263)和(375.744±20.308)nmol/g]和对照组[(3.244±0.275)和(290.935±19.065)nmol/g]显著升高(P<0.05)。持续光照组萎缩基因MAFbx和MuRF-1 mRNA以及下丘脑中TNF-α和IL-1βmRNA的表达水平较规律光照组显著升高(P<0.05),且2组均明显高于对照组(P<0.05)。处于正常光照周期的对照组和规律光照组大鼠,其钟基因BMAL1和CLOCK的表达均具有明显节律性(SE(A)/A<0.3)。BMAL1的表达在光照期开始时最高,而CLOCK在光照期间表达水平高,在黑暗期表达降低。在持续光照组中,BMAL1和CLOCK的表达均失去了节律性(SE(A)/A>0.3)。结论维持正常光照节律可以维持内毒素血症大鼠下丘脑钟基因的正常节律表达,减少POMC介导的骨骼肌消耗,可能对脓毒症的加速康复有一定作用。

Objective Constant light exposure can lead to hypercatabolism.The aim of this study was to investigate the ef-fects of different light rhythm on skeletal muscle metabolism in endotoxemia rats,and looked for the optimal light rhythm that could reduce skeletal muscle consumption and enhance the recovery of patients with sepsis.Methods54 adult male S-D rats were randomly divided into 3 groups on average:Control group(intraperitoneal injection of normal saline+12 h/12 h light-dark cycle for 7 days),LPS-regular light group(intraperitoneal injection of lipopolysaccharide(LPS)+12 h/12 h light-dark cycle for 7 days)and LPS-constant light group(intraperitoneal injection of LPS+constant light for 7 days).All experimental animals were sacrificed on the 8 th day.The level of skeletal muscle metabolites 3-methylhistidine(3-mh)and tyrosine,atrophy genes MAFbx and murf-1 m RNA and hypothalamic clock genes BMAL1,CLOCK and neuropeptide POMC were also de-tected.ResultsThe food intake,weight growth ratio and the ratio of extensor digitorum longus/weight in the LPS-constant light group were significantly lower than those in the LPS-regular light group(P<0.05),and both groups were significantly lower than those in the control group(P<0.01).The skeletal muscle metabolites 3-methylhistidine(nmol/g)and tyrosine(nmol/g)in the LPS-constant light group rats(6.200±0.273 and 461.039±13.292)were significantly higher than those in the LPS-regular light group(5.197±0.263 and 375.744±20.308)and the control group(3.244±0.275 and 290.935±19.065,all P<0.05).The expression levels of atrophic genes MAFbx and murf-1 m RNA and tnf-alpha and il-1 m RNA in hypothalamus in the LPS-constant light group were significantly higher than those in the LPS-regular light group(P<0.05),and both groups were significantly higher than those in the control group(P<0.05).The expression of the clock genes(BMAL1 and CLOCK)in the showed obvious rhythm(SE(A)/A<0.3)in the LPS-regular light group and the control group.The expression of BMAL1 was highest at the beginning of the illumination period,while the expression of CLOCK was high during the illumination period and decreased during the darkness period.In the LPS-constant light group,the expression of BMAL1 and CLOCK rhythm lost rhythm.ConclusionNormal light rhythm can maintain the normal rhythm expression of hypothalamic clock gene in rats with endotoxemia and reduce POMC-mediated skeletal muscle consumption,which may be of positive significance for the enhanced recovery of sepsis.