核因子-κB在烧伤脓毒症大鼠骨骼肌蛋白分解代谢中的作用研究

THE ROLE OF NUCLEAR FACTOR KAPPA B ON SKELETAL MUSCLE PROTEOLYSIS IN BURNED RATS WITH SEPSIS

目的 观察核因子 κB(NF κB)对烧伤脓毒症大鼠骨骼肌蛋白分解代谢的影响 ,并探讨其可能机制。方法 采用 30 %TBSAⅢ度烫伤加内毒素攻击大鼠为模型模拟临床烧伤脓毒症 ,10 5只Wistar大鼠随机分为正常对照组、烧伤脓毒症组、烧伤脓毒症 +NF κB抑制剂二硫代氨基甲酸吡咯烷 (PDTC)组 ,采用凝胶电泳迁移率改变分析法 (EMSA)分析骨骼肌NF κB活性的变化 ,高效液相色谱分析法测定酪氨酸和 3 甲基组氨酸。结果 可见烧伤脓毒症大鼠伸趾长肌总蛋白、肌纤维蛋白降解率在伤后 2h即较对照组即显著升高 ,之后逐渐上升 ,以 12h升高最显著 (P <0 0 1) ;而骨骼肌NF κB的活性于伤后 2h显著升高 ,之后呈现下降趋势 ,伤后 12h其活性仍显著高于正常对照组 (P <0 0 5 )。结论 研究表明NF κB于烧伤脓毒症大鼠的骨骼肌中明显活化 ,而应用NF κB抑制剂PDTC能够明显降低脓毒症时骨骼肌代谢率 ,说明NF κB可能参与调控烧伤脓毒症时骨骼肌的异常代谢。

Objective To observe the role of nuclear factor κB ion skeletal muscle proteolysis in burned rats with sepsis and to evaluate its possible mechanism.Methods RAnimal model, in which rats were subjected to 30% full thickness scald injury followed bycombined with intraperitoneal injection of lipopolysaccharide (LPS), was used for this experiment to mimic early sepsis after burn. One hundred and five Wistar rats were randomly divided into normal control group, burn sepsis group, burn sepsis with Pyrrolidine Dithiocarbamate (PDTC) treatment group. The NF κB activity in extensor digitorum longus (EDL) muscles was determined by electrophoretic mobility shift assay (EMSA). Total and myofibrillar protein breakdown rates were determined by measuring net release of tyrosine and 3 methylhistidine from incubated EDL muscles. Tyrosine and 3 MH were determined by high performance liquid chromatography (HPLC). Results These showed that NF κB activity was markedly activated and reached its peak 2 hourss after the challenge ( P <0 01), then it gradually lowered and was increased at all time points studied. Ttotal and myofibrillar proteolytic rates were upregulated 2 hours after LPS challenge,by sepsis at all time points studied and was progressive during the septic course. and were significant increased at 12 hours as compared with normal control group. After the administration ofusing NF κB inhibitor PDTC, NF κB activity in muscle was markedly decreased, at the same time total and myofibrillar proteolytic rates were also decreased. Conclusion NF κB activity in muscles was upregulated during sepsistic course, and inhibition of NF κB activity ccouldan downregulate the total and myofibrillar proteolytic rates. It is likely that NF κB plays an important role in the modulation of muscle proteolysis during the septic coursesepsis