辣椒素对大鼠心肌缺血再灌注致心肌细胞凋亡的抑制作用

Apoptosis Inhibition of Capsaicin on Myocardial Ischemia-reperfusion Injury in Rats

目的探讨辣椒素在大鼠心肌缺血再灌注实验中是否具有抑制心肌细胞凋亡的作用。方法结扎在体大鼠心脏左冠状动脉前降支45 min,再灌注120 min制备局部心肌缺血再灌注模型。实验分5组,即假手术组、对照组、辣椒素组、辣椒平(辣椒素受体拮抗剂)组和P物质受体拮抗剂组。在缺血前10 min,对照组和辣椒素组左心室予生理盐水,辣椒平组予辣椒平8μg/kg,P物质受体拮抗剂组予S-3144 100μg/kg;除假手术组外,在缺血前5 min,对照组左心室予生理盐水,其余各组予辣椒素4μg/kg,然后进行缺血再灌注处理。监测心率(HR)和左心室发展压(LVDP);光镜下行心肌组织病理观察,TUNEL荧光免疫法检测心肌凋亡阳性细胞核。结果再灌注120 min时辣椒素组HR、LVDP高于对照组、辣椒平组、P物质受体拮抗剂组(P<0.05)。缺血再灌注各组均有大量心肌凋亡细胞核,与假手术组比较差异有统计学意义(P<0.05);辣椒素组凋亡阳性细胞核低于对照组(P<0.05),辣椒平组和P物质受体拮抗剂组与对照组比较无明显差异。结论缺血前应用辣椒素具有抑制心肌细胞凋亡的作用,其机制可能是通过激活辣椒素受体,引起P物质释放,进一步激活NK1型P物质受体起作用的。

Objective To determine apoptosis inhibition effect of capsaicin on myocardial ischemia-reperfusion injury in rats and its underlying mechanisms.Methods The rat model of myocardial ischemia-reperfusion injury was established by ligating the left anterior descending coronary artery for 45 min and then loosing the ligation（reperfusion） for 120 min.Twenty healthy male rats were randomly divided into sham group,control group（I/R）,capsaicin group（CAP＋I/R）,capsazepine group（CAPZ＋CAP＋I/R）,and S-3144 group（S-3144＋CAP＋I/R）.All drugs were delivered bolusly into left ventricle （LV）via right carotid artery at 10 min and 5 min before ischemia.Rats in I/R group and sham group only received vehicle injection.Myocardial protection was assessed by measurements of heart rate（HR） and left ventricular developed pressure （LVDP）.The pathologic changes of myocardial tissue in each group were observed under light microscopy.TUNEL-positive nuclei were tested by immunofluorescent method.Results At 120 min after reperfusion,there were significant increases of HR and LVDP in CAP＋I/R group when compared with control group,capsazepine group,and S-3144 group（P〈0.05）.The apoptotic index in the sham group was lower than that in the groups with ischemia/reperfusion injury（P〈0.05）.Among the groups with ischemia/reperfusion injury,CAP＋I/R group had the lowest apoptotic index（P〈0.05）.ConclusionCAP could generate cardioprotection associated with cardiomyocyte apoptosis inhibition in vivo,likely by stimulating TRPV1 and further activating NK1 receptor.