贝前列素钠预处理对兔心肌缺血/再灌注损伤的早期拮抗作用

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目的:探讨贝前列素钠(beraprost sodium,BPS)预处理对兔心肌缺血/再灌注(I/R)损伤的早期拮抗作用。方法:将36只日本大耳白兔随机分为3组,即A组(假手术组)、B组(I/R组:缺血40 min后,再灌注90 min)和C组(BPS预处理组:以15μg/kg,2次/d,[1]连续喂养4周,最后1次喂养后3 h内进行I/R)。以上3组均开胸暴露心脏,A组在左冠状动脉左室支处穿线不结扎,观察130 min结束实验;B组及C组开胸后结扎左冠状动脉左室支40 min,心电图若出现Ⅱ导联ST段升高及结扎周围心肌的颜色变紫或变深显示已形成心肌梗死(MI)模型。然后进行以下检测:①再灌注90 min后,随机选取6只日本大耳白兔,立即取结扎点下损伤的心肌组织,用100 g/L福尔马林固定后,部分进行HE染色在光镜下观察心肌形态学改变;部分用免疫组化染色法检测心肌细胞中Bax、Bcl-2的表达。②再灌注4 h后,取右心房(或股静脉)血应用电化学发光免疫法检测血浆中心肌中肌酸激酶(CK-MB)的变化。结果:①HE染色显示,A组的心肌结构正常,B组的心肌损伤较严重,C组的心肌损伤较轻。②免疫组化染色法检测显示,A组Bcl-2的表达呈阳性,Bax的表达呈阴性;B组Bax的表达呈强阳性,Bcl-2的表达呈弱阳性;C组Bax的表达呈弱阳性,Bcl-2的表达介于A组与B组之间。③用电化学发光免疫法检测心肌酶学结果,CK-MB升高者3个组依次为B组>C组>A组,B组CK-MB的水平均明显高于C组与A组(P<0.01)。结论:BPS预处理对兔心肌I/R损伤早期具有拮抗作用。 Objective: To investigate the early antagonism of beraprost sodium (BPS) preconditioning on myocardial ischemia / reperfusion (I / R) injury in rabbits. Methods: Thirty - six Japanese white rabbits were randomly divided into three groups: group A (sham operation group), group B (group I / R: 40 min after ischemia, 90 min reperfusion) and group C Treatment groups: I / R was given at 15 μg / kg, 2 times / d, [1] for 4 weeks, and within 3 h after the last feeding. In the above three groups, the heart was opened by thoracotomy. In group A, the left coronary artery branches were not ligated through the left ventricular branches, and the experiment was finished after 130 minutes. Left ventricular branches of the left coronary artery were ligated for 40 minutes after thoracotomy in group B and group C, Elevation of the ST segment of the lead II and the color of the myocardium surrounding the ligature become purple or darker, indicating that a myocardial infarction (MI) model has been established. Then the following tests were carried out: ① After 90 min of reperfusion, six Japanese white rabbits were randomly selected, and the injured myocardial tissue was immediately ligated. After fixation with 100 g / L formalin, HE staining was performed in part The morphological changes of myocardium were observed under microscope. The expression of Bax and Bcl-2 in myocardial cells were detected by immunohistochemistry. ② After 4 h of reperfusion, the changes of creatine kinase (CK-MB) in plasma were detected by chemiluminescence immunoassay in right atrium (or femoral vein) blood. Results: ①HE staining showed that the myocardial structure in group A was normal, the myocardial damage in group B was severe, and the myocardial damage in group C was lighter. ② Immunohistochemical staining showed that the expression of Bcl-2 was positive in group A and the expression of Bax was negative. The expression of Bax in group B was strongly positive and the expression of Bcl-2 was weakly positive. The expression of Bax in group C was weak Positive, Bcl-2 expression between A group and B group. ③ Electrochemiluminescence immunoassay for myocardial enzymology results showed that the CK-MB elevated in three groups followed by B group> C group> A group, B group CK-MB levels were significantly higher than C group and A group P <0.01). Conclusion: Pretreatment with BPS can antagonize the early myocardial I / R injury in rabbits.
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