【作者】 陈元美；

【导师】 郭平凡； 林永堃；

【作者基本信息】 福建医科大学 ， 外科学， 2004， 硕士

【摘要】 目的 应用多西环素阻断基质金属蛋白酶-2和9的功能,探讨基质金属蛋白酶-2和9的功能及其拮抗剂多西环素在骨骼肌缺血再灌注损伤中的作用。方法 24只健康清洁级SD大鼠,随机分为3组,每组8只。A组(对照组):仅行麻醉及颈外静脉插管术;B组(缺血-再灌注组):建立缺血-再灌注损伤前生理盐水灌胃,2ml/次,每日两次,共7天,行左后肢止血带缺血4小时之后,再灌注4小时;C组(处理组):建立缺血-再灌注损伤前多西环素灌胃,50mg/kg,溶于2ml水,每日两次,共7天,左后肢止血带缺血4小时之后,再灌注4小时。研究内容包括:⑴ RT-PCR法测定骨骼肌基质金属蛋白酶-2和9 mRNA表达。⑵比色法检测血浆乳酸脱氢酶(LDH)、肌酸肌酶(CK)、丙二醛(MDA)和组织髓过氧化物酶(MPO)水平,并测定湿重/干重值(W/D)。⑶光电镜观察骨骼肌结构的变化。结果 多西环素能明显降低大鼠骨骼肌缺血再灌注损伤所引起骨骼肌组织基质金属蛋白酶-2和9 mRNA表达;血浆CK、LDH、MDA、组织MPO水平下降;减轻骨骼肌组织结构的破坏。结论 骨骼肌缺血-再灌注激发基质金属蛋白酶-2和9的生成,在介导骨骼肌的损伤中起着重要的作用,多西环素可通过抑制基质金属蛋白酶-2和9的功能减轻SMIRI的损伤程度。更多还原

【Abstract】 objective: Doxycycline, blocking the function of MMP-2 and MMP-9,was used to investigate the role of MMP-2 and MMP-9 and their antagonist,doxycycline, in skeletal muscle ischemia-reperfusion injury(SMIRI). Methods: Twenty-four healthy male Sprague-Dawley rates, weighing 250 to 300g, were selected and randomly devided into group A, B, and C.Rats in the group A underwent anesthetization and external jugμlar vein cannμlation alone; Rats in the group B underwent twice-daily gavage with 2ml normal solution for 7 days prior to the induction of 4h ischemia to the left hindlimb,followed by 4h reperfusion.Rats in the group C were treated by twice-daily gavage with doxycyline (50mg/kg in 2ml water) for 7 days prior to the induction of 4h ischemia to the left hindlimb,followed by 4h reperfusion.Levels of MMP-2 mRNA and MMP-9 mRNA of skeletal muscle were determined by reverse transcription-polymerase chain reaction.The levels of lactate dehydrogenase(LDH), creatine kinase(CK), malondialdehyde(MDA) in the plasma and the myeloperoxidase(MPO) activity in skeletal muscle were measured by colorimetry respectively.The oedema degree was quantified by calculating the wet/dry weight ratio of skeletal muscle.Skeletal muscle were also observed histologically and ultrastructurally.Ruslts: SMIRI contributed to increase the level of MMP-2 and MMP-9 mRNA in skeletal muscle.The level of CK, LDH, MDA, MPO and wet/weight ratio increase significantly. The levels of MMP-2 and MMP-9 mRNA, CK, LDH, MDA, MPO and wet/dry weight ratio were remarkedly decreased after the gavage of doxycycline and thus the pathological injuries were attenuated in skeletal muscles. Conclusion: SMIRI enhanced the synthesis of MMP-2 and MMP-9,which induced the injury of skeletal muscle.Doxycycline reduced SMIRI by blocking the function of <WP=5>MMP-2 and MMP-9.更多还原