脓毒症时骨骼肌细胞糖皮质激素受体表达与低氧诱导因子关系的研究  

Relationship between the expression of glucocorticoid receptor and hypoxia-inducible factor in skeletal muscle cells during sepsis

作　　者：李仁杰[1] 李占飞[1] 白祥军[1] 杨帆[1] 陈驾君[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院创伤外科,湖北武汉430030

出　　处：《创伤外科杂志》2012年第5期443-446,共4页Journal of Traumatic Surgery

摘　　要：目的研究脓毒症时骨骼肌中糖皮质激素受体(GR)表达与低氧诱导因子(HIF-1α)的关系,进一步阐明脓毒症时骨骼肌蛋白高分解代谢的机制。方法 54只Balb/c小鼠随机分为对照组、脓毒症组和治疗组。脓毒症组通过采用腹腔注射脂多糖(10mg/kg)诱导脓毒症(n=24);治疗组(n=24)在伤前2h分别使用糖皮质激素受体拮抗剂(RU38486(10mg/kg)灌胃,余处理同脓毒症组。同时设立对照组(n=6),于伤后24、6、1、2h取材。利用蛋白免疫印迹(western blot)测定肌组织重链肌球蛋白(MHC),半定量逆转录聚合酶链反应(RT-PCR)法检测GR和HIF-1αmRNA的表达变化。结果在内毒素注射6h后,脓毒症小鼠骨骼肌MHC的含量较对照组显著减少,伤前使用糖皮质激素受体拮抗剂RU38486灌胃,于6h后骨骼肌MHC含量增多,后期均高于脓毒症组。脓毒症小鼠GR与HIF-1αmRNA表达在整个实验过程中显著增加;使用RU38486灌胃后,于伤后6h GR mRNA的表达明显降低(P<0.05),并维持在较低水平,在整个治疗过程中HIF-1α明显降低。相关性分析表明,脓毒症中GR与HIF-1α的表达呈正相关。结论体内GR表达增高是脓毒症大鼠骨骼肌蛋白降解显著增加的原因之一,其作用可能是在基因水平与HIF-1α协同作用,进而导致骨骼肌蛋白分解增强。Objective To investigate the relationship between the glucocorticoid receptor and hypoxia-inducible factor 1 alpha（HIF-1α） in skeletal muscle cells during sepsis,and further clarify the mechanism of protein metabolism of skeletal muscle during sepsis.Methods Totally 54 Balb/c mice were randomly divided into control group,sepsis group and treatment group.Totally 24 mice in sepsis group were established by administering lipopolysaccharide（10mg/kg）into peritoneal cavity.Totally 24 mice in treatment group were treated with RU38486（10mg/kg）by gavage 2 hours before administering lipopolysaccharide.While establishing a control group（n=6）,skeletal muscle was acquired at 2,4,6,12 hours after injury.Myosin heavy chain（MHC） of skeletal muscle was determined by western blot.The expression of GR and HIF-1αmRNA was detected by semiquantitative retrovirus polymerase chain reaction（RT-PCR）.Results Comparing with the control group,the MHC content of skeletal muscle in mice with sepsis was reduced significantly 6 hours after injection,however,MHC content in the group treated by RU38486 was higher than sepsis group.The expression of GR and HIF-1α mRNA significantly increased during the whole process;after treatment with RU38486,the expression of GR mRNA reduced markedly（P0.05） and maintained at a very low level at 6 hours after injury.HIF-1α reduced significantly during the treatment course.The correlation analysis showed that the expression of HIF-1α and GR was positively correlated during sepsis.Conclusion The increased GR expression is one of the factors contributing to the significantly increased degradation of skeletal muscle protein during sepsis.This effect may be that the increased GR expression is cooperated with HIF-1α at the genetic level,which causes enhanced decomposing of the skeletal muscle protein.

关 键 词：脓毒症 糖皮质激素受体 低氧诱导因子1Α 骨骼肌 蛋白代谢 

分 类 号：R63[医药卫生—外科学]