咪唑安定保护家兔心肌缺血再灌注损伤机制的研究

Study of Protective Mechanism of Midazolam on Injury of Myocardial Ischemia/Repe rfusion in Rabbits

目的 :观察咪唑安定对家兔心肌缺血 /再灌注期血清和心肌TNF α、IL 6的影响 ,探讨其保护作用机制。方法 :利用结扎 /开放左冠状动脉左前降支 ,结扎 30min/开放 1 80min建立心肌缺血 /再灌注模型。 2 4只家兔随机分为三组 (每组 8只 ) :假手术对照组 (A组 ) ,未予心肌缺血处理 ;缺血再灌注组 (B组 )于缺血前 5min(I0 )、缺血 30min(I1 )、再灌注 1h(R1 )和 3h(R2 )取颈内静脉血 ,并于实验结束后取心肌组织匀浆 ,分别测定IL 6和TNF α浓度 ;咪唑安定组(C组 )缺血前 2 0min静脉注射咪唑安定 0 .75mg/kg(人等效剂量 ) ,以每小时 0 .4mg/kg持续泵入 ,取血样时点和检测指标均同B组。结果 :C组血清TNF α在I1 和R1 时升高 ,R2 时降低 ,IL 6在R2 时升高 ,但在各时点均较B组相应值低 (P <0 .0 1或 0 .0 5 ) ,心肌组织TNF α、IL 6水平亦低于B组 (P <0 .0 5 ) ,但较A组明显升高 (P <0 .0 1 ) ;B组TNF α在I1 时点显著升高 ,IL 6在R1 和R2 时点持续升高 ,心肌组织中TNF α和IL 6含量明显增加 ,同A组和C组比差异有高度显著性。结论 :在心肌缺血再灌注损伤中 ,咪唑安定通过抑制心肌组织和血清TNF α和IL 6的合成或释放 ,从而对心肌组织有保护作用。

To observe the effect of midazolam on TNF α and IL 6 in rabbits serum and myocardium during myocardial ischemia and reperfusion(I /R).Method: Myocardial ischemia and reperfusion(I/R) model was estab lished,and the left anterior descending coronary artery(LAD) was occluded at 30 min/loosen at 180 min.Twenty four rabbits were randomly divided into three grou ps:sham operation group(group A, n=8 );ischemia reperfusion group(group B, n= 8 ) and midazolam group(group C, n=8 ).Rabbits of group B were subjected to o cclusion on the LAD,30 min later followed by reperfusion for 3 h;Group C with mi dazolam administration(0.75 mg·h -1 /kg) 20 min before occlusion and follow ed by 0.4 mg·h -1 /kg.TNF α and IL 6 were measured at the following poin ts:5 min before oc clusion(I 0),30 min after occlusion(I 1),1 h(R 1) and 3 h(R 2) after reperfu sion,and cardiac homogenate.Results: In group C serum TNF α increased at I 1 and R 1,and decreased at R 2,were significantly lower than that of group B( P<0.05 ); serum IL 6 increased at R 2 but lower than that of group B,Myocardial T NF α and IL 6 in group C were obviously lower than those in group B to o( P< 0.05 ).In group B serum TNF α reached it′s peak at R 1 and decreased a little,however, it still higher than that in group A and C ( P< 0.05 ).Serum IL 6 rose obv ious ly at R 1( P< 0.05 ),and were kept at a higher level during reperfusion.Le vels of myocardial TNF α and IL 6 were both higher than those in group A and C( P<0.05) .Conclusion: Midazolam can inhibit the production of serum and my ocardial TNF α and IL 6,then midazolam can protect heart tissue during myocar dial ischemia and reperfusion.