Hall-Angerås M, Angerås U, von Allmen D, Higashiguchi T, Zamir O, Hasselgren P O, Fischer J E
Department of Surgery, University of Cincinnati Medical Center, OH.
Metabolism. 1991 Mar;40(3):247-51. doi: 10.1016/0026-0495(91)90105-6.
We studied the influence of sepsis on muscle protein synthesis and degradation in vivo and in muscles, incubated flaccid or at resting length. Sepsis was induced in rats by cecal ligation and puncture (CLP). Control rats were sham-operated. A flooding dose of 14C-phenylalanine was used to determine muscle protein synthesis rate in vivo, and protein breakdown was calculated from the difference between protein synthesis and growth rates. Protein synthesis rate in vitro was assessed by determining incorporation of 14C-phenylalanine into protein in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles. Total and myofibrillar protein breakdown rates were determined from release into incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Muscle protein synthesis rate in vivo was reduced by 35%, similar to the reduction observed in muscles incubated flaccid or at resting length. The calculated protein breakdown rate in vivo was increased by 31% in septic rats. In incubated muscles, the increase in total protein breakdown (ie, tyrosine release) during sepsis was almost identical in muscles incubated flaccid or at resting length, ie, 83% to 88% in EDL and 47% to 49% in SOL. Myofibrillar protein degradation in vitro (ie, 3-MH release) was increased approximately 10-fold in EDL muscles incubated flaccid or at resting length, but was not significantly affected by sepsis in SOL. Results suggest that sepsis-induced changes in protein synthesis observed in muscles incubated either flaccid or at resting length reflect changes in vivo. Changes in protein breakdown were qualitatively similar in vivo and in vitro, but results in incubated muscles may overestimate the increase in muscle proteolysis caused by sepsis.
我们研究了脓毒症对体内及松弛或处于静息长度状态下肌肉的蛋白质合成与降解的影响。通过盲肠结扎和穿刺（CLP）诱导大鼠发生脓毒症。对照大鼠接受假手术。使用大剂量的14C-苯丙氨酸来测定体内肌肉蛋白质合成速率，并根据蛋白质合成与生长速率之间的差异计算蛋白质分解率。通过测定14C-苯丙氨酸掺入孵育的趾长伸肌（EDL）和比目鱼肌（SOL）中的蛋白质来评估体外蛋白质合成速率。分别根据酪氨酸和3-甲基组氨酸（3-MH）释放到孵育培养基中的量来测定总蛋白和肌原纤维蛋白的分解率。体内肌肉蛋白质合成速率降低了35%，这与在松弛或处于静息长度状态下孵育的肌肉中观察到的降低情况相似。在脓毒症大鼠中，计算得出的体内蛋白质分解率增加了31%。在孵育的肌肉中，脓毒症期间总蛋白分解（即酪氨酸释放）的增加在松弛或处于静息长度状态下孵育的肌肉中几乎相同，即EDL中增加83%至88%，SOL中增加47%至49%。在松弛或处于静息长度状态下孵育的EDL肌肉中，体外肌原纤维蛋白降解（即3-MH释放）增加了约10倍，但在SOL中脓毒症对其没有显著影响。结果表明，在松弛或处于静息长度状态下孵育的肌肉中观察到的脓毒症诱导的蛋白质合成变化反映了体内的变化。体内和体外蛋白质分解的变化在性质上相似，但孵育肌肉的结果可能高估了脓毒症引起的肌肉蛋白水解增加。
