Hasselgren P O, Zamir O, James J H, Fischer J E
Department of Surgery, University of Cincinnati, OH 45267-0558.
Biochem J. 1990 Aug 15;270(1):45-50. doi: 10.1042/bj2700045.
The role of prostaglandins in the regulation of muscle protein breakdown is controversial. We examined the influence of arachidonic acid (5 microM), prostaglandin E2 (PGE2) (2.8 microM) and the prostaglandin-synthesis inhibitor indomethacin (3 microM) on total and myofibrillar protein breakdown in rat extensor digitorum longus and soleus muscles incubated under different conditions in vitro. In other experiments, the effects of indomethacin, administered in vivo to septic rats (3 mg/kg, injected subcutaneously twice after induction of sepsis by caecal ligation and puncture) on plasma levels and muscle release of PGE2 and on total and myofibrillar protein breakdown rates were determined. Total and myofibrillar proteolysis was assessed by measuring production by incubated muscles of tyrosine and 3-methylhistidine respectively. Arachidonic acid or PGE2 added during incubation of muscles from normal rats did not affect total or myofibrillar protein degradation under a variety of different conditions in vitro. Indomethacin inhibited muscle PGE2 production by incubated muscles from septic rats, but did not lower proteolytic rates. Administration in vivo of indomethacin did not affect total or myofibrillar muscle protein breakdown, despite effective plasma levels of indomethacin with decreased plasma PGE2 levels and inhibition of muscle PGE2 release. The present results suggest that protein breakdown in skeletal muscle of normal or septic rats is not regulated by PGE2 or other prostaglandins.
前列腺素在调节肌肉蛋白质分解中的作用存在争议。我们研究了花生四烯酸（5微摩尔）、前列腺素E2（PGE2）（2.8微摩尔）和前列腺素合成抑制剂吲哚美辛（3微摩尔）对在不同体外条件下孵育的大鼠趾长伸肌和比目鱼肌中总蛋白和肌原纤维蛋白分解的影响。在其他实验中，测定了吲哚美辛对脓毒症大鼠（3毫克/千克，在盲肠结扎和穿刺诱导脓毒症后皮下注射两次）体内血浆PGE2水平、肌肉PGE2释放以及总蛋白和肌原纤维蛋白分解率的影响。分别通过测量孵育肌肉中酪氨酸和3-甲基组氨酸的生成来评估总蛋白水解和肌原纤维蛋白水解。在正常大鼠肌肉孵育期间添加花生四烯酸或PGE2，在多种不同体外条件下均未影响总蛋白或肌原纤维蛋白降解。吲哚美辛抑制了脓毒症大鼠孵育肌肉中PGE2的生成，但并未降低蛋白水解率。尽管吲哚美辛在血浆中的有效水平使血浆PGE2水平降低且抑制了肌肉PGE2释放，但体内给予吲哚美辛并未影响总蛋白或肌原纤维蛋白的分解。目前的结果表明，正常或脓毒症大鼠骨骼肌中的蛋白分解不受PGE2或其他前列腺素的调节。
