白细胞介素-1介导骨骼肌缺血再灌注损伤的研究

Skeletal muscle ischemia reperfusion injury mediated by interleukin-1

目的 探讨白细胞介素 1(IL 1)介导大鼠骨骼肌缺血再灌注损伤的作用及其机制。方法 2 4只健康雄性SD鼠 ,随机分为假手术组 :仅行颈外静脉插管术 ;损伤组 :缺血 4h ,再灌注 4h ;干预组 :缺血 4h ,再灌注即刻经静脉导管给与白细胞介素 1受体拮抗剂 (IL 1ra)。采用逆转录 聚合酶链反应 (RT PCR)法测定骨骼肌和肺组织白细胞介素 1β(IL 1β)mRNA表达 ;酶联免疫吸附试验法 (ELISA)测定血浆IL 1β水平 ;比色法检测血浆乳酸脱氢酶 (LDH)、肌酸激酶 (CK )、丙二醛(MDA)和组织过氧化物酶 (MPO )含量及电镜观察组织超微结构的改变。结果 应用IL 1ra后 ,IL 1βmRNA水平明显降低 (骨骼肌 :0 .73± 0 .3 5较 1.2 0± 0 .42 ,P <0 .0 1;肺 :1.15± 0 .2 3较 1.70±0 .3 0 ,P <0 .0 1) ;血浆IL 1β水平显著下降(P <0 .0 1) ;CK (76.77± 18.2 8较 12 7.0 7± 2 8.3 4,P <0 .0 1)、LDH (165 40 .85± 10 2 0 .63较 2 3 3 70 .61± 2 160 .5 4,P <0 .0 1)、MDA (7.2 2± 1.65较 9.73±1.91,P <0 .0 1)和MPO (骨骼肌 :2 .2 4± 0 .3 8较 4.43± 0 .65 ,P <0 .0 1;肺 :1.13± 0 .16较 2 .71±0 .3 2 ,P <0 .0 1)含量均明显降低 ,骨骼肌和肺组织超微结构损伤减轻。结论 骨骼肌缺血 再灌注激发IL 1的生成 ,在介导骨?

Objective To explore the mechanism of interleukin 1 mediating skeletal muscle ischemia reperfusion (SMIR) injury.Methods Twenty four healthy male Sprague Dawley rates,weighing 250 to 300 g,were selected and randomly divided into groups A,B,C.Group A underwent external jugular vein cannulation alone (sham),group B underwent left hindlimb ischemia for 4 h,followed by reperfusion for 4 h (control),and group C also underwent ischemia and reperfusion,but was treated intravenously with interleukin 1 receptor antagonist (2 mg/kg) at the time of reperfusion (treatment).The levels of IL 1β mRNA in skeletal muscle and lung were determined by reverse transcription polymerase chain reaction.Enzyme linked immum osorbent assay was performed for plasma levels of IL 1β.The levels of creatine kinase (CK),lactate dehydrogenase (LDH),malondialdehyde (MDA) and myeloperoxidase (MPO) activity in skeletal muscle and lung were measured by colorimetry respectively.Results The interleukin 1 receptor antagonist significantly decreased the level of IL 1β mRNA (skeletal muscle: 0.73± 0.35 vs 1.20± 0.42, P < 0.01; lung: 1.15± 0.23 vs 1.70± 0.30, P < 0.01), so did the level of IL 1β in the plasma ( P < 0.01). In addition,the levels of CK (76.77± 18.28 vs 127.07± 28.34, P < 0.01), LDH (16?540.85± 1?020.63 vs 23?370.61± 2?160.54, P < 0.01), MDA (7.22± 1.65 vs 9.73± 1.91, P < 0.01) and MPO (skeletal muscle: 2.24± 0.38 vs 4.43± 0.65, P < 0.01; lung: 1.13± 0.16 vs 2.71± 0.32, P < 0.01) were decreased significantly ( P < 0.01). The pathological lesions in skeletal muscle and lung were attenuated.Conclusion IL 1 mediates an injurious effect on skeletal muscle and lung during skeletal muscle ischemia reperfusion injury.