Glucose Infusion Suppresses Surgery-induced Muscle Protein Breakdown by Inhibiting Ubiquitin-proteasome Pathway in Rats
Glucose Infusion Suppresses Surgery-induced Muscle Protein Breakdown by Inhibiting Ubiquitin-proteasome Pathway in Rats
复制标题
DOI：
10.1097/aln.0b013e318190b6c1
复制
发表时间：
2009-01-01
期刊：
影响因子：
8.8
通讯作者：
Nikawa, Takeshi
中科院分区：
文献类型：
--
作者：
Mikura, Mayumi;Yamaoka, Ippei;Nikawa, Takeshi
背景：众所周知，手术后蛋白质分解代谢会加速，而葡萄糖输注会抑制分解代谢反应。然而，术后早期手术应激和葡萄糖输注对肌肉蛋白分解代谢的影响及相关机制尚不清楚。方法：给剖腹手术的大鼠输注不含葡萄糖（对照）或含1%或5%葡萄糖的醋酸林格氏液（10 ml.kg(-1).h(-1)）。手术治疗后继续输注4小时。测定分解代谢指数、尿氮和3-甲基组氨酸的排泄以及离体肌肉中酪氨酸和3-甲基组氨酸的释放。此外，还评估了蛋白水解相关基因（atrogin-1/MAFbx、肌肉环指-1、mu-和 m-钙蛋白酶、组织蛋白酶 L 和 H）的肌肉 mRNA 表达以及胰岛素信号成分（叉头盒 O3 和蛋白激酶 B）的磷酸化。 结果：手术增加了分解代谢指数，而这种增加被葡萄糖输注（1% 和 5%）所抑制。在对照组中，atrogin-1/MAFbx 和肌肉环指-1 的 mRNA 表达增加，而在两个葡萄糖组中则受到抑制。此外，葡萄糖输注会刺激肌肉中的胰岛素信号传导（蛋白激酶 B 和叉头盒 O3 的磷酸化）。结论：本研究表明，即使输注速度相对较低，葡萄糖输注也能抑制术后早期的肌肉蛋白质分解。这种作用的机制与泛素-蛋白酶体途径的抑制有关，并伴有胰岛素信号传导的激活。
Background: It appears to have been well established that after surgery, protein catabolism is accelerated and glucose infusion suppresses the catabolic reactions. However, in the early postoperative period, the effects of surgical stress and glucose infusion on muscle protein catabolism and the related mechanisms remain unclear.Methods: Rats undergoing laparotomy were infused with acetated Ringer's solution (10 ml.kg(-1).h(-1)) without glucose (control) or containing 1% or 5% glucose. The infusion was continued for a further 4 h after the surgical treatment. The catabolic index, excretion of urinary nitrogen and 3-methylhistidine, and release of tyrosine and 3-methylhistidine from isolated muscle were determined. Furthermore, muscular mRNA expression of proteolytic-related genes (atrogin-1/MAFbx, muscle ring finger-1, mu- and m-calpain, and cathepsin L and H) and phosphorylation of components of insulin signaling (forkhead box O3 and protein kinase B) were evaluated.Results: Surgery increased the catabolic index, and this increase was suppressed by glucose infusion (both 1% and 5%). in the control group, mRNA expression of atrogin-1/MAFbx and muscle ring finger-1 was increased, and they were suppressed in the two glucose groups. Furthermore, insulin signaling (phosphorylation of protein kinase B and forkhead box O3) in muscles was stimulated by glucose infusion.Conclusion: The present study indicates that glucose infusion, even at a relatively low rate, suppresses muscle protein breakdown in the early postoperative period. The mechanism of this effect is related to the suppression of the ubiquitin-proteasome pathway, accompanied by activation of insulin signaling.