烫伤早期TNFα与IL-1增强骨骼肌蛋白质分解代谢作用机制的研究

Mechanism of TNFα and IL-1 enhancing protein catabolism in skeletal muscles of mice in early stage after severe burn

目的 观察严重烫伤小鼠早期TNFα与IL 1对骨骼肌蛋白质分解代谢的影响及其机制。方法 建立包括背部及一侧后肢 18%～ 2 0 %Ⅲ度体表烫伤小鼠模型。以比目鱼肌体外温育酪氨酸净释放量反映骨骼肌蛋白质分解速率 ,观察 72h内伤肢、未伤肢骨骼肌蛋白质分解速率 ,以及血浆、伤肢、未伤肢TNFα与IL 1含量及溶酶体组织蛋白酶类活性的动态变化。结果 伤后小鼠血浆、伤肢、未伤肢TNFα与IL 1水平均显著增高 ,48h达到峰值 ,伤肢增高更为明显 ,72h已见回落。未伤肢蛋白质分解速率 48h高于正常 ,但 72h已降至正常水平 ,伤肢则在 72h明显高于正常与未伤肢 ,骨骼肌溶酶体组织蛋白酶活性与分解速率呈明显正相关。hrTNFα与hrIL 1分别对正常小鼠在体和离体比目鱼肌均可导致蛋白质分解速率与溶酶体组织蛋白酶活性增高。结论 烫伤早期TNFα、IL 1增强溶酶体内组织蛋白酶的活性导致骨骼肌蛋白质分解代谢的过度增强 ,从而造成机体负氮平衡是直接的 ,可能不受激素影响。

Objective To observe the effects and mechanism of TNFα and IL 1 on protein catabolism of skeletal muscles of mice in the early stage of severe burn. Methods A BALB/c mice model was established with full thickness scalded of 18%～20% TBSA including the back and one hind limb. The catabolic rate of protein of soleus muscle was reflected with the net tyrosine releasing rate. The changes of the tyrosine releasing rates of the injured and uninjured limbs, the levels of TNFα and IL 1 of the plasma and soleus muscle, and the activities of lysosomal proteolytic enzymes were observed in 72 h after scald injury of the mice. Results After injury, the levels of TNFα and IL 1 of plasma, injured and uninjured limbs were all increased, and reached the summit at the 48th h, but those of the injured limb were much higher than those of the uninjured one, then gradually the levels were decreased in 72 h. The protein catabolic rate of uninjured limb was higher than the normal at h 48, but it came to normal level at h 72. The rate of the injured limb was higher than that of normal and uninjured limbs significantly 72 h after the scalding. hrTNFα and hrIL 1 enhanced the protein catabolic rate and the activities of lysosomal protrolytic enzymes in the soleus muscle of normal mice in vivo and in vitro respectively. Conclusion In the early stage of scald injury, TNFα and IL 1 could enhance the lysosomal protease activity, increase the protein catabolic rate in skeletal muscle and promote the negative nitrogen balance directly. These effects may not depend on the actions of emergent hormones.