大蒜素和前列地尔注射液防治急性心肌梗塞再灌注后无复流的实验研究
摘要
目的:评价和探讨大蒜素注射液和微脂质体前列地尔防治猪急性心肌梗死再灌注无复流现象的作用和机制。
方法:中华小型猪随机分成假手术组(6只)、模型组(8只)、大蒜素组(8只)和前列地尔组(8只)。后三组经左冠状动脉前降支球囊闭塞2h后再灌注3h制备PTCA术后无复流模型。急性心肌梗塞前、后和再灌注1h、2h、3h后进行血流动力学测定、心肌声学造影、血清学放免检测,最终进行病理染色。摘取不同区域心肌组织后,通过相对定量Real-time PCR、Western-blotting、免疫组化和HE染色,检测黏附分子及内皮细胞功能相关因子的变化。
结果:大蒜素注射液和前列地尔微脂球体注射液明显恢复左室收缩压和降低左室舒张压,缩小无复流区面积(P＜0.05)。这两者能够通过降低GM-CSF、整合素β1、PECAM-1、VCAM、PDGF、E-选择素和P-选择素的mRNA合成(P＜0.05)及整合素β1、PECAM-1和PDGF受体的蛋白表达,减少了白细胞、血小板的聚集和黏附,从而有效地抑制了缺血/再灌注损伤,减少微血栓的形成。此外,大蒜素和微脂球体前列地尔能够上调VEGF和eNOS的mRNA合成和蛋白表达(P＜0.05),从而改善微血管内皮细胞功能,产生NO而扩张血管。
结论:大蒜素和前列地尔从抑制白细胞、血小板黏附作用和改善微循环功能等方面发挥作用,缩小了无复流区域面积,有效地防治了急性心肌梗塞再灌注治疗后无复流现象的发生。
Objective To evaluate and discuss the effects and mechanism of Garlicin injection and Lipo-PGE1 injection on myocardial no-reflow in a mini-swine model with acute myocardial infarction(AMI) and reperfusion and to research the related mechanism.
Methods:The mini-swines were randomized into four study groups:six in sham-operated group,eight in control group,eight in Garlicin injection-treated group and eight in Lipo-PGE1 injection-treated group.The mini-swines in the latter three groups were subjected to the left anterior descending(LAD) coronary occlusion by dilated balloon for two hours and then reperfursion for three hours to make the no-refiow model after percutaneous transluminal coronary angioplasty.Before AMI, at two hours after AMI and at one,two,three hours after reperfusion,the data on hemodynamics was examined by means of the catheter,the blood serum and plasma were examined by the radio-immunity analysis and the area of no-reflow was respectively evaluated with the myocardial contrast echocardiography(MCE) in vivo and pathological staining means.After selecting the myocardial issue in different regions,the change on the adhesion molecules and other molecules related to the effects of endothelial cell was detected by relative quantitive real-time PCR, Western-blotting,immunohistochemistry and HE staining.
Results:The areas of no-reflow region were reduced by the Garlicin injection and Lipo-PGE1 injection(P＜0.05) and the left ventricular systolic pressure(LVSP) and left ventricular end-diastolic pressure(LVEDP) were restored.The adhesion and aggregation of polymorphonuclear leucocyte and platelet were lessened to inhibit the ischemia/reperfursion injury and the thrombosis by lowering the mRNA expression of GM-CSF,PECAM-1,Intergrinβ1,VCAM-1,PDGF,E-selectin and P-selectin and the protein synthesis of PECAM-1,PDGF receptor and Intergrinβ1(P＜0.05).In addition, the mRNA expression and protein synthesis of VEGF and eNOS were upregulated (P＜0.05) by Garlicin injection and Lipo-PGE1 injection to ameliorate the function of endothelial cell in coronary capillary and product NO to dilate the capillary.
Conclustions:The Garlicin injection and Lipo-PGE1 injection had exerted the certain effect on inhibitting the adhension of plathet and leukocyte and ameliorating the function of minicirculation to reduce the area of no-reflow and effectively provent and treat the no-reflow phenomenon after reperfusion treatment of the acute myocardial infarction.
方法:中华小型猪随机分成假手术组(6只)、模型组(8只)、大蒜素组(8只)和前列地尔组(8只)。后三组经左冠状动脉前降支球囊闭塞2h后再灌注3h制备PTCA术后无复流模型。急性心肌梗塞前、后和再灌注1h、2h、3h后进行血流动力学测定、心肌声学造影、血清学放免检测,最终进行病理染色。摘取不同区域心肌组织后,通过相对定量Real-time PCR、Western-blotting、免疫组化和HE染色,检测黏附分子及内皮细胞功能相关因子的变化。
结果:大蒜素注射液和前列地尔微脂球体注射液明显恢复左室收缩压和降低左室舒张压,缩小无复流区面积(P＜0.05)。这两者能够通过降低GM-CSF、整合素β1、PECAM-1、VCAM、PDGF、E-选择素和P-选择素的mRNA合成(P＜0.05)及整合素β1、PECAM-1和PDGF受体的蛋白表达,减少了白细胞、血小板的聚集和黏附,从而有效地抑制了缺血/再灌注损伤,减少微血栓的形成。此外,大蒜素和微脂球体前列地尔能够上调VEGF和eNOS的mRNA合成和蛋白表达(P＜0.05),从而改善微血管内皮细胞功能,产生NO而扩张血管。
结论:大蒜素和前列地尔从抑制白细胞、血小板黏附作用和改善微循环功能等方面发挥作用,缩小了无复流区域面积,有效地防治了急性心肌梗塞再灌注治疗后无复流现象的发生。
Objective To evaluate and discuss the effects and mechanism of Garlicin injection and Lipo-PGE1 injection on myocardial no-reflow in a mini-swine model with acute myocardial infarction(AMI) and reperfusion and to research the related mechanism.
Methods:The mini-swines were randomized into four study groups:six in sham-operated group,eight in control group,eight in Garlicin injection-treated group and eight in Lipo-PGE1 injection-treated group.The mini-swines in the latter three groups were subjected to the left anterior descending(LAD) coronary occlusion by dilated balloon for two hours and then reperfursion for three hours to make the no-refiow model after percutaneous transluminal coronary angioplasty.Before AMI, at two hours after AMI and at one,two,three hours after reperfusion,the data on hemodynamics was examined by means of the catheter,the blood serum and plasma were examined by the radio-immunity analysis and the area of no-reflow was respectively evaluated with the myocardial contrast echocardiography(MCE) in vivo and pathological staining means.After selecting the myocardial issue in different regions,the change on the adhesion molecules and other molecules related to the effects of endothelial cell was detected by relative quantitive real-time PCR, Western-blotting,immunohistochemistry and HE staining.
Results:The areas of no-reflow region were reduced by the Garlicin injection and Lipo-PGE1 injection(P＜0.05) and the left ventricular systolic pressure(LVSP) and left ventricular end-diastolic pressure(LVEDP) were restored.The adhesion and aggregation of polymorphonuclear leucocyte and platelet were lessened to inhibit the ischemia/reperfursion injury and the thrombosis by lowering the mRNA expression of GM-CSF,PECAM-1,Intergrinβ1,VCAM-1,PDGF,E-selectin and P-selectin and the protein synthesis of PECAM-1,PDGF receptor and Intergrinβ1(P＜0.05).In addition, the mRNA expression and protein synthesis of VEGF and eNOS were upregulated (P＜0.05) by Garlicin injection and Lipo-PGE1 injection to ameliorate the function of endothelial cell in coronary capillary and product NO to dilate the capillary.
Conclustions:The Garlicin injection and Lipo-PGE1 injection had exerted the certain effect on inhibitting the adhension of plathet and leukocyte and ameliorating the function of minicirculation to reduce the area of no-reflow and effectively provent and treat the no-reflow phenomenon after reperfusion treatment of the acute myocardial infarction.
引文
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