CAJ | 학술논문

目的结扎左冠状动脉前降支建立大鼠急性心肌梗死(AMI)模型,比较血管内皮生长因子(VEGF)、胎盘生长因子(PLGF)以及VEGF+ PLGF联合应用对急性心肌缺血后心功能的改善作用,探讨其治疗心肌梗死后左心室重构的可行性,以及应用抗VEGF受体1、2(αVEGFR1、αVEGFR2)抗体拮抗VEGF和PLGF的修复信号对心肌梗死后心功能的影响.方法 90只Wistar大鼠,数字表法随机分为9组:伪手术组、模型组、VEGF组、PLGF组、VEGF+PLGF组、αVEGFR1组、αVEGFR2组、αVEGFR1+αVEGFR2组及免疫球蛋白2a(IgG2a)对照组,每组10只.除伪手术组大鼠外,其余大鼠均结扎左冠状动脉前降支(LAD)建立急性心肌梗死模型,并于心肌梗死区域注射给药.术后2周,观测大鼠心功能,经股静脉注射15％ KCl 2 ml处死大鼠,快速切取心脏,石蜡包埋,病理切片评估左心室结构,免疫组化检测vW因子和α平滑肌肌动蛋白(αSMA)分析心肌梗死区域的新生血管,TUNEL实验分析心肌梗死区心肌细胞凋亡情况.结果 PLGF组和VEGF+ PLGF组AMI大鼠的心功能得到有效改善,显著抑制左心室重构及心肌细胞凋亡;VEGF组无明显作用;抗体封闭VEGFR1和VEGFR2未对AMI大鼠心功能造成恶化.LAD结扎的大鼠心肌梗死区总血管密度与伪手术组相比均显著提高,其中VEGF组、PLGF组及VEGF+PLGF组的总血管密度较AMI模型组和其余药物干预组显著提高;只有PLGF或VEGF+PLGF能提高左心室动脉密度,其余实验组未发现动脉密度改变.综合实验数据,VEGF+ PLGF组大鼠心肌梗死区的血管和动脉最为丰富,左心室重构最轻微,心功能改善最显著.结论早期应用PLGF或VEGF+PLGF能显著改善AMI大鼠心功能,同等剂量VEGF未能显著改善心功能;应用抗体封闭VEGFR1和VEGFR2未造成AMI大鼠心功能进一步衰竭,提示有其他因素参与左心室重构及冠状动脉血运重建.
목적 결찰좌관상동맥전강지건립대서급성심기경사(AMI)모형,비교혈관내피생장인자(VEGF)、태반생장인자(PLGF)이급VEGF+ PLGF연합응용대급성심기결혈후심공능적개선작용,탐토기치료심기경사후좌심실중구적가행성,이급응용항VEGF수체1、2(αVEGFR1、αVEGFR2)항체길항VEGF화PLGF적수복신호대심기경사후심공능적영향.방법 90지Wistar대서,수자표법수궤분위9조:위수술조、모형조、VEGF조、PLGF조、VEGF+PLGF조、αVEGFR1조、αVEGFR2조、αVEGFR1+αVEGFR2조급면역구단백2a(IgG2a)대조조,매조10지.제위수술조대서외,기여대서균결찰좌관상동맥전강지(LAD)건립급성심기경사모형,병우심기경사구역주사급약.술후2주,관측대서심공능,경고정맥주사15％ KCl 2 ml처사대서,쾌속절취심장,석사포매,병리절편평고좌심실결구,면역조화검측vW인자화α평활기기동단백(αSMA)분석심기경사구역적신생혈관,TUNEL실험분석심기경사구심기세포조망정황.결과 PLGF조화VEGF+ PLGF조AMI대서적심공능득도유효개선,현저억제좌심실중구급심기세포조망;VEGF조무명현작용;항체봉폐VEGFR1화VEGFR2미대AMI대서심공능조성악화.LAD결찰적대서심기경사구총혈관밀도여위수술조상비균현저제고,기중VEGF조、PLGF조급VEGF+PLGF조적총혈관밀도교AMI모형조화기여약물간예조현저제고;지유PLGF혹VEGF+PLGF능제고좌심실동맥밀도,기여실험조미발현동맥밀도개변.종합실험수거,VEGF+ PLGF조대서심기경사구적혈관화동맥최위봉부,좌심실중구최경미,심공능개선최현저.결론 조기응용PLGF혹VEGF+PLGF능현저개선AMI대서심공능,동등제량VEGF미능현저개선심공능;응용항체봉폐VEGFR1화VEGFR2미조성AMI대서심공능진일보쇠갈,제시유기타인소삼여좌심실중구급관상동맥혈운중건.
Objective AMI is a prevalent global health condition.This study assessed the effects of PLGF and VEGF in a rat model of post-AMI.Methods Wistar rats underwent LAD ligation and injection of VEGF,PLGF,VEGF + PLGF,antiVEGFR1,anti-VEGFR2,anti-VEGFR1 + anti-VEGFR2,IgG2α,or saline,into the infarct border zone.We also set up a pseudo-operation group.Two weeks later,heart function was detected by hemodynamic and geometry,then the hearts were dis sected and HE stained.We assessed vW factor and α-SMA by immunohistochemistry and cardiomyocyte apoptosis rate by TUNEL.Results Rats in the VEGF + PLGF group performed significantly well in cardiac function,had weaker LV remodeling and less cardiomyocyte apoptosis.There were no obvious changes in VEGF group.The use of VEGFR1/VEGFR2 antibody didnt deteriorate the rat's cardiac function.More new-born arteries were seen in PLGF and VEGF + PLGF rats,and change wasnt found in other groups.Lastly,the most angiogenesis,the least left ventricular remodeling and the best heart function were observed in VEGF + PLGF group.Conclusion Earlier intervention with PLGF or VEGF + PLGF can improve heart function in rats with AMI; VEGF alone didnt improve heart function.VEGFR1/VEGFR2 antibody didnt aggravate the rat's heart function.This indicates that left ventricular and coronary remodeling may involve other factors.