急性心肌缺血对小鼠大脑血流灌注量影响的实验研究

Effects of acute myocardial ischemia on cerebral blood flow perfusion in mice

目的 心脏功能指标迅速恶化所引起的脑血流灌注量的改变可能对脑功能产生较大影响。文章观察心肌缺血小鼠心脏功能、脑血流灌注量和血管舒缩功能的变化,探讨急性心肌缺血(AMI)所致脑血流低灌注状态的可能原因。方法采用结扎冠状动脉左前降支法复制急性心肌缺血小鼠模型。小鼠按照完全随机法分为正常组、AMI组,每组各10只。心超检测观察心率(HR)、左心室射血分数(LVEF)、短轴缩短率(LVFS)、每搏输出量(SV)和心输出量(CO)变化;激光散斑血流成像观察脑血流灌注曲线和单位时间内的血流灌注量变化;ELISA检测各组心肌与脑组织中的内皮素1(ET-1)与降钙素基因相关肽(CGRP)的含量变化,并采用线性相关和回归分析比较相关指标之间的相互关系。结果 与正常组比较,AMI组小鼠LVEF、LVFS、SV和CO显著下降(P<0.001),单位时间内脑血流灌注量显著下降(P<0.001),心肌与脑组织中ET-1含量显著升高(P<0.01、P<0.05),CGRP含量无显著性差异(P>0.05)。线性相关分析提示,LVEF、LVFS、SV和CO均与脑血流灌注量呈正相关且具有统计学意义(R^(2)=0.520 7,P<0.01;R^(2)=0.479 7,P<0.01;R^(2)=0.603 8,P<0.01;R^(2)=0.655 1,P<0.01);心肌组织的CGRP与脑组织的CGRP呈正相关且具有统计学意义(R^(2)=0.499 8,P<0.01),心肌组织的ET-1与脑组织的ET-1呈负相关且具有统计学意义(R^(2)=0.603 9,P<0.01);脑组织ET-1含量与脑血流灌注量呈负相关,CGRP含量与脑血流灌注量呈正相关且均具有统计学意义(R^(2)=0.231 9,P<0.05;R^(2)=0.265 8,P<0.05)。结论 AMI小鼠心脏功能异常可能导致心肌组织和脑组织的血管舒缩物质ET-1和CGRP含量产生变化,引起脑血管低灌注的症状。

Objective The changes of cerebral blood flow perfusion caused by the rapid deterioration of cardiac function indexes may have a great influence on brain function. To observe the changes of cardiac function, cerebral blood flow perfusion and vasomotor function in mice with myocardial ischemia, and to explore the possible causes of cerebral blood flow hypoperfusion caused by acute myocardial ischemia(AMI). Methods The mouse model of AMI was established by ligating the left anterior descending branch of coronary artery. Mice were randomly divided into normal group(n=10) and AMI group(n=10). The changes of heart rate(HR), left ventricular ejection fraction(LVEF), short axis fractional shortening(LVFS), stroke volume(SV) and cardiac output(CO) were observed by echocardiography, and the changes of cerebral blood flow perfusion curve and blood flow volume per unit time were observed by laser speckle imaging. The contents of endothelin 1(ET 1) and calcitonin gene-related peptide(CGRP) in myocardium and brain tissue of each group were detected by ELISA, and the relationship between related indexes was compared by linear correlation and regression analysis. Results Compared with the normal group, LVEF, LVFS, SV and CO in AMI group decreased significantly(P<0.001), cerebral blood flow perfusion decreased significantly(P<0.001), and the content of ET 1 in myocardium and brain tissue increased significantly(P<0.01), but the content of CGRP had no significant difference(P>0.001). Linear correlation analysis showed that LVEF, LVFS, SV and CO were positively correlated with cerebral blood flow perfusion(R^(2)=0.520 7, P<0.01;R^(2)=0.479 7, P<0.01;R^(2)= 0.603 8, P<0.01;R^(2)=0.655 1, P<0.01) and with statistical significance. The CGRP of myocardial tissue was positively correlated with that of brain tissue(R^(2)=0.4998, P<0.01). The ET 1 of myocardial tissue was positively correlated with that of brain tissue(R^(2)=0.603 9, P<0.01). The content of ET 1 in brain tissue was negatively correlated with the volume of cerebral blood flow perfusion, while the content of CGRP was positively correlated with the volume of cerebral blood flow perfusion(R^(2)=0.231 9, P<0.05;R^(2)=0.265 8, P<0.05) with statistical significance. Conclusion The abnormal cardiac function in mice with AMI may result in the changes of the contents of the vasomotor substances ET 1 and CGRP in myocardium and brain tissue, and cause the symptoms of cerebral vascular hypoperfusion.