白细胞介素-1受体拮抗剂对骨骼肌缺血再灌注损伤的保护作用

Experimental Study of Interleukin-1 Receptor Antagonist Against Skeletal Muscle Ischemia-Reperfusion Injury

目的 观察白细胞介素 - 1受体拮抗剂 (IL- 1Ra)对大鼠骨骼肌缺血再灌注损伤的影响。 方法 2 4只健康清洁级 SD大鼠 ,随机分为 3组。对照组 :仅行颈外静脉插管术 ;模型组 :缺血 4 h再灌注 4 h;处理组 :缺血 4 h再灌注即刻静脉导管给予 IL- 1Ra。采用酶联免疫吸附试验 (EL ISA)法、比色法测定血浆白细胞介素 - 1β(IL- 1β)、肿瘤坏死因子 - α(TNF- α)、组织髓过氧化物酶 (MPO) ,免疫组织化学法检测组织血管内皮细胞间粘附分子 - 1(ICAM- 1)的表达及电镜观察组织超微结构的改变。 结果 应用 IL- 1Ra能使血浆 IL- 1β、TNF- α水平显著下降(P<0 .0 1)。组织 MPO含量 (骨骼肌 :2 .13± 0 .38vs4 .31± 0 .5 7,P<0 .0 1;肺 :0 .96± 0 .0 8vs2 .6 5± 0 .2 4 ,P<0 .0 1)和血管内皮细胞 ICAM- 1表达明显下降 ,组织损伤减轻。 结论 IL-

Objective\ To investigate the effect of interleukin\|1 receptor antagonist(IL\|1Ra) on skeletal muscle ischemia\|reperfusion injury.\ Methods\ 24 healthy male Sprague\|Dawley rates, weighing 250～300 g, were selected and randomly devided into group A, B, C.\ Group A underwent external jugular vein cannulation alone(sham).\ Group B underwent 4 hours of left hindlimb ischemia followed by 4 hours of reperfusion(control).\ 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).\ Standard assays were performed for plasma levels of IL\|1, TNF\|α.\ The myeloperoxidase(MPO) activity in skeletal muscle and lung were measured by colorimetry respectively.\ The expression of intercellular adhesion molecule\|1(ICAM\|1) in vascular endothelium was assessed by immunohistochemistry.\ The ultrastructural changes of the skeletal muscle and lung were observed with electron microscopy.\ Results\ Skeletal muscle ischemia reperfusion(SMIR) showed significant increase of the levels of IL\|1β, TNF\|α in plasma(P<0 01).\ IL\|1Ra reduced the increased levels of IL\|1β, TNF\|α in plasma(P<0 01).\ SMIR showed in a distinct increase in the level of MPO.\ However, treatment with IL\|1Ra significantly lowered the level of MPO(skeletal muscle: 2 13±0 38 vs 4 31±0 57,P<0 01; lung:0 96±0 08 vs 2 65±0 24,P<0 01).\ ICAM\|1 expression in endothelium of skeletal muscle and lung were markedly downregulated by IL\|1Ra.\ The damage to the ultrastructure of skeletal muscle and lung were alleviated after IL\|1Ra treatment.\ Conclusion\ IL\|1Ra plays an important role in the protection of skeletal muscle with reperfusion injury