银杏酮酯与丹参预处理对心肌缺血再灌注中环氧化酶-2及其下游效应物的作用

Effect of Precondition with GBE50 and Salviae miltionrrhizae on Cycloxygenase-2 and Its Downstream Effectors Contents in Ischemia/Reperfusion Myocardium

目的探讨大鼠心肌缺血再灌注后环氧化酶-2(COX-2)及其下游效应物含量的变化,并观察银杏酮酯(Ginkgo biloba extract50,GBE50)与丹参预处理对其的影响。方法大鼠分为假手术组、模型组、丹参组及GBE50低、高中剂量组。各组动物灌胃GBE50或丹参注射液1周后,结扎冠脉左前降支30min,再灌注60min建立大鼠心肌缺血再灌注模型。实时荧光定量PCR检测心肌COX-2表达;放射免疫法检测心肌血栓烷B2(TXB2),6-酮-前列腺素F1α(6-keto-PGF1α)含量。结果模型组COX-2mRNA水平明显高于假手术组(P<0.001);与模型组比较,GBE50与丹参可明显下调心肌COX-2基因表达(P<0.01),并降低心肌TXB2含量与TXB2/PGF1α比值(P<0.05),丹参还可上调心肌6-keto-PGF1α含量(P<0.05)。结论缺血再灌注后,COX-2通过产物血栓素A2(TXA2)和前列环素(PGI2)对心肌产生作用,GBE50与丹参对COX-2的生成均有抑制作用,且两者的作用可能不同。

Objective To investigate the changes in contents of cycloxygenase-2（COX-2）and its downstream effectors in rat＇s myocardial ischemia/reperfusion（I/R）model and observe the effects of precondition with GBE50（Ginkgo biloba extract 50）and Salviae miltiorrhizae（SM）on them.Methods Rat＇s I/R model was established by 30-min left anterior descending coronary artery occlusion followed with 60-min reperfusion.Animals were divided into the model control group,the sham-operated group and the tested groups（received 1-week precondition with GBE50 and SM respectively via intragastric infusion before modeling）.COX-2 mRNA expression in myocardium was detected by real-time PCR;contents of thromboxane B2（TXB2）and 6-keto-prostaglandin F1α（6-keto-PGF1α）were measured by radioimmunoassay.Results The mRNA expression of COX-2 in the model group was obviously higher than that in the sham-operated group（P0.001）,while that in the tested groups was down-regulated significantly（P0.01）,and the content of TXB2 as well as the ratio of TXB2/PGF1α was reduced significantly（P0.05）.Besides,SM also showed the up-regulation effect on 6-keto-PGF1α content in myocardium（P0.05）.Conclusion COX-2 affects the myocardium through thromboxane A2 and prostacyclin after I/R;both GBE50 and SM can inhibit the production of COX-2,but they may act in different paths.