Clark A S, Kelly R A, Mitch W E
J Clin Invest. 1984 Sep;74(3):888-97. doi: 10.1172/JCI111506.
Negative nitrogen balance and increased oxygen consumption after thermal injury in humans and experimental animals is related to the extent of the burn. To determine whether defective muscle metabolism is restricted to the region of injury, we studied protein and glucose metabolism in forelimb muscles of rats 48 h after a scalding injury of their hindquarters. This injury increased muscle protein degradation (PD) from 140 +/- 5 to 225 +/- 5 nmol tyrosine/g per h, but did not alter protein synthesis. Muscle lactate release was increased greater than 70%, even though plasma catecholamines and muscle cyclic AMP were not increased. Insulin dose-response studies revealed that the burn decreased the responsiveness of muscle glycogen synthesis to insulin but did not alter its sensitivity to insulin. Rates of net glycolysis and glucose oxidation were increased and substrate cycling of fructose-6-phosphate was decreased at all levels of insulin. The burn-induced increase in protein and glucose catabolism was not mediated by adrenal hormones, since they persisted despite adrenalectomy. Muscle PGE2 production was not increased by the burn and inhibition of prostaglandin synthesis by indomethacin did not inhibit proteolysis. The increase in PD required lysosomal proteolysis, since inhibition of cathepsin B with EP475 reduced PD. Insulin reduced PD 20% and the effects of EP475 and insulin were additive, reducing PD 41%. An inhibitor of muscle PD, alpha-ketoisocaproate, reduced burn-induced proteolysis 28% and lactate release 56%. The rate of PD in muscle of burned and unburned rats was correlated with the percentage of glucose uptake that was directed into lactate production (r = +0.82, P less than 0.01). Thus, a major thermal injury causes hypercatabolism of protein and glucose in muscle that is distant from the injury, and these responses may be linked to a single metabolic defect.
人类和实验动物热损伤后出现的负氮平衡和耗氧量增加与烧伤程度有关。为了确定肌肉代谢缺陷是否仅限于损伤区域，我们研究了大鼠后肢烫伤48小时后前肢肌肉中的蛋白质和葡萄糖代谢。这种损伤使肌肉蛋白质降解（PD）从140±5增加到225±5 nmol酪氨酸/克每小时，但未改变蛋白质合成。尽管血浆儿茶酚胺和肌肉环磷酸腺苷未增加，但肌肉乳酸释放增加了70%以上。胰岛素剂量反应研究表明，烧伤降低了肌肉糖原合成对胰岛素的反应性，但未改变其对胰岛素的敏感性。在所有胰岛素水平下，净糖酵解和葡萄糖氧化速率增加，6-磷酸果糖的底物循环减少。烧伤诱导的蛋白质和葡萄糖分解代谢增加并非由肾上腺激素介导，因为肾上腺切除术后这些反应仍持续存在。烧伤并未增加肌肉前列腺素E2的产生，吲哚美辛抑制前列腺素合成也未抑制蛋白水解。PD的增加需要溶酶体蛋白水解，因为用EP475抑制组织蛋白酶B可降低PD。胰岛素使PD降低20%，EP475和胰岛素的作用是相加的，使PD降低41%。肌肉PD抑制剂α-酮异己酸使烧伤诱导的蛋白水解降低28%，乳酸释放降低56%。烧伤和未烧伤大鼠肌肉中的PD速率与进入乳酸生成的葡萄糖摄取百分比相关（r = +0.82，P < 0.01）。因此，严重热损伤会导致远离损伤部位的肌肉中蛋白质和葡萄糖的分解代谢亢进，这些反应可能与单一代谢缺陷有关。
