重组人胰岛素样生长因子Ⅰ对大鼠成骨细胞增殖、凋亡及Ⅰ型胶原蛋白合成的影响

目的 观察胰岛素样生长因子Ⅰ（IGF-Ⅰ）对体外培养的大鼠成骨细胞的增殖、凋亡及Ⅰ型胶原蛋白合成的影响，探讨IGF-Ⅰ对骨代谢影响的可能机制。方法 不同浓度rhIGF-Ⅰ刺激体外培养的大鼠成骨细胞，采用噻唑蓝（MTT）法测定细胞增殖能力；肿瘤坏死因子α（TNF-α单独或与rhIGF-Ⅰ共同刺激成骨细胞，流式细胞仪检测细胞周期和凋亡率；rhIGF-Ⅰ刺激成骨细胞，免疫细胞化学结合计算机图像分析系统检测Ⅰ型胶原蛋白的表达。结果 一定浓度IGF-Ⅰ能明显增加成骨细胞数量（P〈0．05），在0．1～100ng／ml这种作用与IGF-Ⅰ的浓度呈正相关；TNF-α在0．1～100ng/ml浓度范围内呈剂量依赖性地促进成骨细胞凋亡（P〈0．05），并使S期细胞减少（P〈0．05），而IGF-Ⅰ能抑制，TNF-α对成骨细胞的促凋亡作用（P〈0．05）；经IGF-Ⅰ的刺激，成骨细胞Ⅰ型胶原蛋白的表达明显高于对照组（P〈0．05）。结论 IGF-Ⅰ对大鼠成骨细胞有明显的促增殖作用，在0．1～100ng/ml之间呈浓度依赖性，IGF-Ⅰ能抑制，TNF-α诱导的大鼠成骨细胞凋亡，IGF-Ⅰ能促进大鼠成骨细胞Ⅰ型胶原蛋白的合成。     

胰岛素样生长因子Ⅰ对臂丛神经损伤后骨骼肌细胞凋亡的影响

目的研究胰岛素样生长因子Ⅰ(IGF-Ⅰ)抑制臂丛神经损伤后失神经肱二头肌萎缩及其对骨骼肌细胞凋亡的影响.方法采用成年Wister大鼠,建立右侧臂丛神经损伤的动物模型,IGF-Ⅰ治疗组术后于右侧肱二头肌内注射rhIGF-Ⅰ,用量为200mg/kg-1·3d-1,对照组术后于右侧肱二头肌内注射生理盐水.5周后观察比较肱二头肌湿重,采用TUNEL法检测肱二头肌肌细胞的凋亡率.结果IGF-Ⅰ治疗组骨骼肌湿重为(509.4±92.3)mg,肌细胞凋亡率为(28.4±9.5)%;对照组骨骼肌湿重为(461.8±48.1)mg,肌细胞凋亡率为(54.5±12.1)%.经统计学分析均具有非常显著的差异.结论臂丛神经损伤后肱二头肌内局部注射rhIGF-Ⅰ能够有效地减缓其萎缩.rhIGF-Ⅰ抑制失神经肌细胞凋亡是原因之一.     

大鼠创伤后胰岛素抵抗与葡萄糖转运关系的研究

目的探讨创伤后骨骼肌对葡萄糖转运能力的改变及其与创伤后胰岛素抵抗（m）之间的关系。方法通过对大鼠实施小肠部分切除手术建立创伤模型，观察大鼠血糖和血清胰岛素浓度的变化规律。运用高胰岛素-正常血糖钳夹技术评估外周组织葡萄糖廓清率。[^3H]标记葡萄糖示踪法检测创伤后骨骼肌葡萄糖转运能力的变化。最后分别测定大鼠骨骼肌组织中葡萄糖转运蛋白-4（GLUT-4）的mRNA和蛋白表达。结果大鼠小肠部分切除术后血糖浓度明显升高，血清胰岛素浓度则先短暂降低然后升高。创伤组大鼠外周组织对葡萄糖的廓清率下降了47％（P〈0．01）。创伤组大鼠骨骼肌对葡萄糖的转运能力明显低于对照组（P〈0．01）。两组大鼠骨骼肌中GLUT4mRNA和GLUT-4蛋白总量的表达差异无统计学意义（P〉0．05），但是创伤组大鼠骨骼肌细胞膜上的GLUT-4蛋白含量明显少于对照组（P〈0．05）。结论大鼠手术后早期即存在胰岛素抵抗现象，但胰岛素分泌量并未减少。创伤后早期骨骼肌细胞膜上GLUT-4分布减少以及对葡萄糖转运能力降低可能是导致创伤后胰岛素抵抗的机制之一。     

胰岛素样生长因子Ⅰ对臂丛神经损伤后骨骼肌细胞凋亡的影响

目的:研究胰岛素样生长因子Ⅰ(IGF-Ⅰ)抑制臂丛神经损伤后失神经肱二头肌萎缩及其对骨骼肌细胞凋亡的影响。方法:采用成年Wister大鼠,建立右侧臂丛神经损伤的动物模型,IGF-Ⅰ治疗组:术后于右侧肱二头肌内注射rh IGF-Ⅰ,用量为200mg/kg~(-1)·3d~(-1),对照组:术后于右侧肱二头肌内注射生理盐水。5周后观察比较肱二头肌湿重,采用TUNEL法检测肱二头肌肌细胞的凋亡率。结果:IGF-Ⅰ治疗组骨骼肌湿重为(509.4±92.3)mg,肌细胞凋亡率为(28.4±9.5)％;对照组骨骼肌湿重为(461.8±48.1)mg,肌细胞凋亡率为(54.5±12.1)％。经统计学分析均具有非常显著的差异。结论:臂丛神经损伤后肱二头肌内局部注射rh IGF-Ⅰ能够有效地减缓其萎缩。rhIGF-Ⅰ抑制失神经肌细胞凋亡是原因之一。     

生长激素、营养支持与恶性肿瘤

生长激素是由垂体前叶嗜酸细胞合成、贮存和释放：其释放率受下丘脑的生长激素释放激素（GHRH）的刺激控制。生长激素通过直接作用和间接作用[通过体内合成胰岛素样生长因子-1(IGF-1)],来发挥其刺激蛋白质合成、促进生长发育、刺激脂肪分解及其储存等作用。生长激素刺激蛋白质合     

不同类型老年女性髋部骨折血清IGF-1及IGFBP-3,4,5表达相关性研究

目的研究不同类型老年女性髋部骨折中外周血清中血清胰岛素样生长因子1（IGF-1）及血清胰岛素样生长因子结合蛋白3,4,5（IGFBP-3,4,5）表达差异及同骨密度的相关性。方法选取年龄大于65岁老年女性髋部骨折患者,检测并比较外周血清中IGF-1及IGFBP-3,4,5表达差异及同骨密度的相关性。结果转子间骨折组转子区骨矿物质密度（BMD）较股骨颈骨折组低（P〈0.001）,股骨颈组血清中IGFBP-4含量较转子间骨折组低（P〈0.001）,而IGFBP-5含量高于转子间骨折组（P〈0.001）。在血清指标相关性表达中,血清IGF-1表达与股骨颈区BMD成正相关（R=0.46,P=0.002）,血清IGFBP-4同转子区BMD成负相关（R=-0.634,P〈0.001）,血清IGFBP-5同股骨颈区BMD成正相关（R=0.235,P〈0.001）。结论外周血清中IGF-1及其结合蛋白表达的差异可能是导致不同类型老年髋部骨折的病理机制之一,但由于IGF-1及其结合蛋白调节机制相当复杂,对于IGF-1及IGFBPs表达机制同骨折类型的关系尚需大量的实验研究进一步证实。     

胰岛素样生长因子-I与老年女性糖尿病患者骨密度关系的研究

目的 探讨老年女性糖尿病患者骨密度及血清胰岛素样生长因子-Ⅰ（IGF-Ⅰ）的变化及其相互关系。方法 用双能X线骨密度仪分别测定老年女性糖尿病患者骨密度值；用酶联免疫的方法测定受试者血清IGF-Ⅰ的水平，并与正常对照组比较。结果 老年女性2型糖尿病组骨质疏松（OP）发病率高于对照组（P〈0．05）；血清IGF-Ⅰ水平低于对照组（P〈0．05）；糖尿病伴OP组血清IGF-Ⅰ低于无OP组（P〈0．05）；糖尿病患者骨密度值与血清IGF-Ⅰ水平显著正相关（P〈0，05）。结论 老年女性2型糖尿病组OP发病率增高，与IGF-Ⅰ水平降低导致骨形成减少有关。     

补肾方对流产大鼠胎盘胰岛素样生长因子介导孕激素生成的影响

目的探讨补肾方对流产大鼠胎盘胰岛素样生长因子Ⅰ、Ⅱ（IGF—Ⅰ、IGF-Ⅱ）及其受体（R）在胎盘滋养层细胞表达的影响及其与孕激素分泌的关系。方法溴隐亭皮内注射法建立流产大鼠模型,于孕1～8、1～11d灌服补肾方药,孕酮（P）肌注作为阳性对照组,采用放射免疫法测定大鼠血清P水平;逆转录聚合酶链反应（RT-PCR）技术检测IGF-Ⅰ、IGF-Ⅱ及其受体在不同组大鼠胎盘中的mRNA表达。结果溴隐亭模型组IGF-Ⅰ、IGF-Ⅱ、IGF-Ⅱ RmRNA表达比正常对照组显著降低（P〈0．01）;中药组及P组降低IGF-ⅠRmRNA表达,并不同程度提高模型大鼠胎盘IGF-Ⅰ、IGF-Ⅱ、IGF-ⅡR mRNA表达。表达强度随孕龄和给药时间逐渐升高,且与血清P有相关。结论补肾方益气清热、固肾安胎,可调控胎盘滋养细胞IGF-Ⅰ、IGF-Ⅱ及其受体的基因表达,并且调节滋养层细胞的增殖活性,促进P合成分泌增加,从而达到保胎的目的。     

氨基酸溶液和重组人生长激素对肝硬化大鼠生长激素-胰岛素样生长因子1轴的影响

目的探讨氨基酸溶液和重组人生长激素(rhGH)对肝硬化大鼠生长激素(GH)-胰岛素样生长因子1(IGF—1)轴的影响。方法肝硬化大鼠随机分为术前组、肝部分切除后1d组、术后肠外营养用复方氨基酸注射液(Novamin)5d组、用10％复方氨基酸注射液(Hepa)5d组、用rhGH Hepa 5d组,各组均为6只大鼠,对照组为正常大鼠。分别测大鼠肝功能、血糖及血清GH、IGF-1、胰岛素样生长因子结合蛋白3(IGFBP-3)水平,用逆转录聚合酶链反应检测肝白蛋白(ALB) mRNA、IGF-1 mRNA、IGFBP-3m RNA的表达,肝组织行Ki67免疫组化染色。结果用Hepa的肠外营养组5d后与用Novamin组比较,GH水平明显降低,肝ALB mRNA、IGF-1m RNA、IGFBP-3 mRNA表达水平明显升高,肝Ki67指数无差别;而rhGH Hepa组肠外营养5d后比Hepa组血糖、GH、IGF-1、IGFBP-3水平明显升高,肝ALB mRNA、IGF-1 mRNA表达水平及肝Ki67指数也明显升高。结论氨基酸溶液和重组人生长激素均可影响肝硬化大鼠生长激素．胰岛素样生长因子1轴,检测血清IGF-1、IGFBP-3水平有助于营养素的选择和评估。     

重组生长激素对肾病综合征大鼠血清蛋白的影响

目的:观察基因重组生长激素(rhGH)对肾病综合征大鼠(NS大鼠)血清总蛋白、白蛋白和胰岛素样生长因子-1(IGF-1)的作用.方法:制备阿霉素大鼠NS模型,设正常组(6只)、模型组 (12只)和rhGH治疗组 (12只).以放射免疫法(RIA)测血清IGF-1水平,用酶联免疫吸附试验测尿微量白蛋白浓度(Alb),S-丽春红测 24 h尿蛋白定量,全自动生化仪测量血清总蛋白和白蛋白.结果:模型组大鼠血清蛋白、血清IGF-1浓度均显著低于正常组.rhGH治疗4周时血清IGF-1和血清蛋白与模型组大鼠同期相比显著上升;而rhGH治疗组与模型组同期尿蛋白排出无统计学差异.结论:NS时,尿蛋白排出量增加和血清GH/IGF-1轴紊乱导致血清蛋白水平下降,外源性rhGH在不增加尿蛋白排出的情况下可提高NS血清IGF-1和蛋白水平.     

血清胰岛素样生长因子1与肾病大鼠生长障碍的关系

目的探讨营养不良、肾病本身和糖皮质激素作为各自独立因素对大鼠血清胰岛素样生长因子1(IGF-1)浓度的影响,阐明血清IGF-1代谢紊乱与肾病综合征(NS)大鼠生长障碍的关系。方法24只周龄相同体重相近的雄性SD大鼠被随机分成正常对照、食物对照、阿霉素肾病和地塞米松治疗的阿霉素肾病4组。血清IGF-1浓度和肝脏ICF-1Mrna表达分别采用放射免疫(RIA)和逆转录-聚合酶链反应(RT-PCR)法检测。结果1．食物对照和肾病组大鼠较正常组血清IGP-1明显减低,肝脏IGF-1Mrna表达明显增高,但两组间差异显著性学意义。2．激素治疗组大鼠较肾病组血清IGF-1及肝脏IGF-1Mrna表达均显著下降。3．血清IGF-1浓度与大鼠鼻-尾长度和体重均呈正相关(P＜0．01)。结论肾病综合征生长障碍归因于继发性营养不良所致的血清IGF-1浓度减低,糖皮质激素治疗则通过进一步减低血清IGF-1浓度使生长障碍加剧。     

Protein synthesis and degradation in skeletal muscle of chronically uremic rats

We used the perfused hemicorpus preparation to measure individual rates of protein synthesis and degradation. Using fed animals, perfused either with or without insulin, muscle protein synthesis and hemicorpus protein degradation rates were similar, but myofibrillar protein degradation was clearly increased in the uremic preparations. When the animals were fasted, differences in the rates of skeletal muscle protein turnover were apparent. Uremic rats lost more wt at both 24 and 48 hr of fasting when compared to either ad libitum fed or pair-fed controls who started fasting at body wts equivalent to our uremic rats. The accelerated wt loss was accompanied by lower rates of protein synthesis, higher degradation rates, and greater net protein catabolism in our uremic rats. Alterations in body lipid content were present in uremia and correlated with the rate of protein degradation in both control and uremic rats. These data demonstrated that even in the fed state, uremia is associated with subtle alterations in skeletal muscle protein turnover. When stressed, these alterations become more pronounced. Insufficient stores of body lipids, either due to inadequate nutrition or altered metabolism, may contribute to the alterations in muscle protein turnover seen in chronic renal insufficiency.     

慢性压迫性脊髓损伤后大鼠运动功能及周围神经和骨骼肌中胰岛素样生长因子-1表达的变化

目的 观察慢性压迫性脊髓损伤后大鼠运动功能变化及周围神经和骨骼肌中胰岛素样生长因子-1(IGF-1)表达变化.方法 将50只Wistar雌性大鼠随机分为正常组、假手术组和慢性压迫组.慢性压迫组置入平头塑料螺钉对大鼠脊髓进行后路渐进性压迫,于2个月后分别压迫至20%、40%、60%左右程度.行神经功能观察;处死大鼠后取腓肠肌作为标本,分别进行IGF-1的免疫组织化学和原位杂交染色.结果 大鼠后肢瘫痪程度随压迫程度加重而加重,各组坐骨神经和骨骼肌中IGF-1蛋白和mRNA表达分别为:20%组(236.9±3.2)、(231.5±2.9)、(245.6±3.4)、(246.6±2.7);40%组(205.3±2.7)、(202.2±3.4)、(209.4±2.6)、(214.6±2.5);60%组(215.4±3.5)、(219.3±4.1)、(231.9±2.3)、(238.5±2.7).各压迫组坐骨神经及骨骼肌中IGF-1 mRNA和蛋白表达增加,与正常组比较差异有统计学意义(P<0.05).结论脊髓压迫性损伤可引起周围神经及骨骼肌中IGF-1表达增加,提示机体调动保护因素以减轻脊髓损伤并促进其再生.

Abstract：

Objective To observe the changes in motor function and expression of insulin-like growth factor-1 (IGF-1) of peripheral nerve and skeletal muscle in rats after chronic spinal cord compression. Methods A total of 50 Wistar rats were randomly divided into normal group (n=10), sham operation group (group A,n=10) and chronic compressive group (goup B,n=30). The rats in group B were given gradual compression on the posterior spinal cord using blunt plastics screw. Compression degree reached 20% (n=10), 40% (n=10) and 60% (n=10) respectively after two months. The rats were killed, and gastrocnemius muscle cells were removed. The expression levels of IGF-1 protein and mRNA in peripheral nerve and skeletal muscle were detected by immunohistochemistry and hybridization respectively after chronic compressive spinal cord injury. Results The rat hind limb paralysis was exacerbated with the increase of the compression. In the sciatic nerve and skeletal muscle, the expression levels of IGF-1 protein and mRNA were: (236.9±3.2), (231.5±2.9), (245.6±3.4), (246.6±2.7) in 20% group; (205.3±2.7), (202.2±3.4), (209.4±2.6), (214.6±2.5) in 40% group; (215.4±3.5), (219.3±4.1), (231.9±2.3), (238.5±2.7) in 60% group. The expression levels of IGF-1 protein and mRNA in peripheral nerve and skeletal muscle were significantly up-regulated after compression (P<0.05). Conclusion The results indicate that body transfers the protective factor to relieve injury of CNS.     

Acidosis, not azotemia, stimulates branched-chain, amino acid catabolism in uremic rats

To investigate branched-chain, amino acid metabolism (BCAA) in muscle in chronic renal failure (CRF), we studied rats with moderately severe uremia (PUN 110 approximately mg/dl) and spontaneous metabolic acidosis (bicarbonate, 19 +/- 1 mEq/liter). Plasma BCAA levels in CRF compared to pair-fed control rats were approximately 15% lower and muscle valine was 93 microM lower (P less than 0.05). BCAA metabolism was measured in incubated epitrochlearis muscles using L-[1-14C]valine or L-[1-14C]leucine in the presence and absence of insulin. BCAA decarboxylation was increased (P less than 0.05) and insulin-stimulated BCAA incorporation into protein was blunted (P less than 0.05) by CRF. Since we have found that metabolic acidosis, by itself, stimulates muscle branched-chain, ketoacid dehydrogenase activity, another group of CRF and control rats was given NaHCO3 which corrected the acidosis, but not the azotemia. BCAA decarboxylation in muscle was reduced in CRF rats given NaHCO3, and this was reflected in increased plasma and muscle BCAA concentrations. We conclude that in CRF, chronic metabolic acidosis stimulates BCAA decarboxylation in skeletal muscle and this could contribute to the reduced intra- and extracellular concentrations of BCAA. Correction of acidosis should be a goal of therapy in CRF, especially when dietary regimens restrict intake of BCAA.     

Changes of protein metabolism in liver and skeletal muscle following trauma complicated by sepsis

The effects of trauma (laparotomy) and trauma complicated by sepsis (laparotomy and ligation and puncture of the cecum) on protein metabolism in liver and skeletal muscle were studied in rats. Unoperated animals served as controls. Rate of amino acid incorporation into proteins was determined in incubated liver slices and bundles of muscle fibers. Proteolysis in skeletal muscle was measured as release of tyrosine from incubated muscle biopsies. Protein synthesis in liver tissue was increased by 42% following trauma and by 164% following trauma and sepsis. In skeletal muscle amino acid incorporation into proteins was reduced by 50% in both conditions while protein degradation was enhanced by about 70%. Thus when injury was complicated by sepsis the metabolic response was augmented in liver but not in skeletal muscle. One reason for this difference might be that changes of protein metabolism in trauma and sepsis are regulated by different mechanisms in liver and skeletal muscle. The results also indicate that increased amino acid supply from peripheral protein breakdown is not the only signal for enhanced hepatic protein synthesis in trauma and sepsis.     

Protein metabolism in different types of skeletal muscle during early and late sepsis in rats

Protein synthesis and degradation rates were measured in incubated soleus (SOL) and extensor digitorum longus (EDL) muscles 4, 8, and 16 hours following cecal ligation and puncture (CLP) in rats. No significant differences in protein synthesis between septic and control rats were found. The proteolytic rate in SOL muscle was increased by 36% eight hours after CLP and by 42% 16 hours after CLP. In EDL muscle, protein breakdown was not significantly increased until 16 hours after CLP, at which time it was 53% above the control value. The plasma amino acid pattern became increasingly deranged during the course of the study, and at 16 hours almost all individual amino acid levels were significantly different in septic rats compared with control rats. There was a significant positive correlation between plasma concentrations of phenylalanine, histidine, and ornithine and the proteolytic rate in EDL and SOL muscles, with the best correlation being found between phenylalanine concentration and proteolytic rate in SOL muscle. These results suggest that muscle wasting during sepsis is caused by increased protein breakdown, not by decreased protein synthesis, and that accelerated muscle proteolysis is an early phenomenon in sepsis.     

Effects of acute and chronic uremia on active cation transport in rat myocardium

As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously (J Clin Invest 81:1197, 1988). Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, [3H]ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity [3H]ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.     

Downregulation of intestinal cytochrome p450 in chronic renal failure

Chronic renal failure (CRF) is associated with a decrease in intestinal drug metabolism. The mechanisms remain poorly understood, but one hypothesis involves a reduction in cytochrome P450 levels. This study aimed to investigate the effects of CRF on intestinal cytochrome P450. Two groups of rats were defined, i.e., rats with CRF (induced by 5/6 nephrectomy) and control pair-fed rats. Total cytochrome P450 levels and protein and mRNA expression of cytochrome P450 isoforms, as well as in vitro N-demethylation of erythromycin (a probe for CYP3A activity) and 7-ethoxyresorufin o-deethylase activity (a probe for CYP1A), were assessed in intestinal microsomes. Body weights were similar in the two groups. Creatinine clearance was reduced by 77% (P < 0.001) in CRF rats, compared with control pair-fed animals. Total intestinal cytochrome P450 activity was reduced by 32% (P < 0.001) in CRF rats. CYP1A1 and CYP3A2 protein expression was considerably reduced (>40%, P < 0.001) in rats with CRF. CYP2B1, CYP2C6, and CYP2C11 levels were the same in the two groups. RT-PCR assays revealed marked downregulation of CYP1A1 and CYP3A2 gene expression in CRF rats (P < 0.001). Although intestinal cytochrome P450 levels were reduced in CRF, induction by dexamethasone was present. N-Demethylation of erythromycin and 7-ethoxyresorufin o-deethylase activity were decreased by 25% (P < 0.05) in CRF rats, compared with control rats. In conclusion, CRF in rats is associated with decreases in intestinal cytochrome P450 activity (mainly CYP1A1 and CYP3A2) secondary to reduced gene expression.     

Inhibition of skeletal muscle protein synthesis in septic intra-abdominal abscess

Chronic sepsis is always associated with profound wasting leading to increased release of amino acids from skeletal muscle. Net protein catabolism may be due to decreased rate of synthesis, increased rate of degradation, or both. To determine whether protein synthesis is altered in chronic sepsis, the rate of protein synthesis in vivo was estimated by measuring the incorporation of [3H]-phenylalanine in skeletal muscle protein in a chronic (5-day) septic rat model induced by creation of a stable intra-abdominal abscess using an E. coli + B. fragilis-infected sterile fecal-agar pellet as foreign body nidus. Septic rats failed to gain weight at rates similar to control animals, therefore control animals were weight matched to the septic animals. The skeletal muscle protein content in septic animals was significantly reduced relative to control animals (0.18 +/- 0.01 vs. 0.21 +/- 0.01 mg protein/gm wet wt; p less than 0.02). The rate of incorporation of [3H]-phenylalanine into skeletal muscle protein from control animals was 39 +/- 4 nmole/gm wet wt/hr or a fractional synthetic rate of 5.2 +/- 0.5%/day. In contrast to control animals, the fractional synthetic rate in septic animals (2.6 +/- 0.2%/day) was reduced by 50% compared to control animals (p less than 0.005). The decreased rate of protein synthesis in sepsis was not due to an energy deficit, as high-energy phosphates and ATP/ADP ratio were not altered. This decrease in protein synthesis occurred even though septic animals consumed as much food as control animals.(ABSTRACT TRUNCATED AT 250 WORDS)