Macallan D C, Cook E B, Preedy V R, Griffin G E
Division of Infectious Diseases, St. George's Hospital Medical School, London, U.K.
Int J Biochem Cell Biol. 1996 May;28(5):511-20. doi: 10.1016/1357-2725(95)00170-0.
Sepsis is associated with net breakdown of skeletal muscle protein, mediated partly by reduced rates of muscle protein synthesis. This study investigated the role of altered gene expression for specific muscle proteins in mediating reduced protein synthesis in a rat model of acute severe sepsis. Adult rats were given a single sublethal intraperitoneal dose of endotoxin (bacterial lipopolysaccharide). Protein, RNA and DNA contents of muscle were measured and changes in expression of mRNA in tibialis anterior and extensor digitorum longus muscles were detected by quantification of Northern blots at 6, 24, 48 and 72 hr after endotoxin and in animals starved for 24 hr. Results showed that at 24 hr after endotoxin there was a loss of about 14% of muscle protein content. No reduction in mRNA was found at any time point for beta-myosin heavy chain (MHC), fast-MHC, alpha-actin, skeletal muscle troponin or carbonic anhydrase III (CA III); rather, at 48 hr there was increased expression of beta-MHC (224 +/- 123% control) and CA III (202 +/- 56%). Blocking TNF-alpha by pre-treatment with a monoclonal antibody did not appear to influence this. Total RNA content of muscle was reduced to 67% of the control values 24 hr after LPS, although this was no different to pair-fed animals starved for 24 hr. It is concluded that reduced protein synthesis in skeletal muscle in early acute sepsis is not primarily associated with reduced muscle protein gene expression.
脓毒症与骨骼肌蛋白质的净分解代谢有关，部分原因是肌肉蛋白质合成速率降低。本研究在急性重症脓毒症大鼠模型中，探讨特定肌肉蛋白基因表达改变在介导蛋白质合成减少中的作用。成年大鼠单次腹腔注射亚致死剂量的内毒素（细菌脂多糖）。测量肌肉的蛋白质、RNA和DNA含量，并通过对内毒素注射后6、24、48和72小时以及饥饿24小时的动物的胫前肌和趾长伸肌中mRNA表达的Northern印迹定量检测。结果显示，内毒素注射后24小时，肌肉蛋白质含量损失约14%。在任何时间点，β-肌球蛋白重链（MHC）、快肌MHC、α-肌动蛋白、骨骼肌肌钙蛋白或碳酸酐酶III（CA III）的mRNA均未减少；相反，在48小时时，β-MHC（224±123%对照）和CA III（202±56%）的表达增加。用单克隆抗体预处理阻断TNF-α似乎并未影响这一结果。脂多糖注射后24小时，肌肉总RNA含量降至对照值的67%，尽管这与饥饿24小时的配对喂养动物没有差异。结论是，急性早期脓毒症时骨骼肌蛋白质合成减少主要与肌肉蛋白质基因表达降低无关。
