原花青素B2改善大鼠急性心肌梗死心室结构和功能的分子机制

Molecular mechanism of procyanidin B2 improving ventricular structure and function in rats with acute myocardial infarction

目的观察不同质量浓度的原花青素B2(PCB2)对大鼠急性心肌梗死后的心室结构和功能的影响及其分子机制。方法采用结扎左冠状动脉前降支方法建立大鼠急性心肌梗死模型作为Model组,以每天2、4、8 mg·Kg^(-1)的原花青素B2诱导干预急性心肌梗死模型大鼠(PCB2-L组、PCB2-M组、PCB2-H组),同时设立假手术组(Sham组)和阳性对照卡托普利(captopril,CAP)组。在连续处理28 d后检测各组大鼠的心功能指标;HE染色检测各组大鼠心肌组织变化和心肌横截面积(cross section area,CAS)变化;Real-time PCR检测大鼠心肌组织肥厚及纤维化标志物基因表达水平;Tunel法检测各组大鼠心肌梗死组织中心肌细胞凋亡;酶联免疫吸附法(ELISA)检测各组大鼠外周血中心肌相关炎性因子水平变化。结果与Sham组相比,各PCB2干预组大鼠的LVSP均逐渐下降(P<0.05),而LVEDP、+dp/dtmax和-dp/dtmax均逐渐上升(P<0.05);各PCB2干预组心肌组织细胞均有不同程度的病理改善,其心肌细胞CAS值逐渐降低(P<0.05);各PCB2干预组大鼠心肌细胞中ANP、BNP、β-MHC和胶原蛋白Ⅰ、胶原蛋白Ⅲ、CTGF基因表达水平均逐渐降低(P<0.05);而各PCB2干预组大鼠心肌细胞凋亡率均逐渐降低(P<0.05);各PCB2干预组大鼠外周血中心肌相关炎性因子(VCAM-1、MCP-1、ICAM-1、TNF-α、IL-6)水平均逐渐降低(P<0.05),接近于CAP作用组。结论PCB2能够明显改善急性心肌梗死后心室重构和心肌功能,可通过抑制心肌细胞肥大、纤维化、凋亡发挥作用,并与其抑制心肌相关炎性因子有关。

This study was performed to investigate the effects of different concentrations of proanthocyanidin B2(PCB2)on ventricular structure and function after acute myocardial infarction in rats and its molecular mechanisms.Acute myocardial infarction model of rats was established by ligating the anterior descending branch of the left coronary artery.Rats of acute myocardial infarction model were treated with procyanidin B2 at 2,4,and 8 mg·kg^(-1)·d^(-1) respectively,and designated as PCB2-L group,PCB2-M group,PCB2-H group.Sham group and positive control captopril(CAP)group were also established.Cardiac function indexes of rats in each group were detected after 28 days of continuous treatment.HE staining was used to detect the changes of myocardial tissue and myocardial cross-sectional area(CAS)in rats of each group;real-time PCR was used to detect the expression levels of cardiac hypertrophy and fibrosis marker genes in rat myocardial tissue.The apoptosis of myocardial cells in myocardial infarction tissues of rats was detected by Tunel method;ELISA was used to measure myocardial associated inflammatory factors concentration changes in the peripheral blood samples of the rats.Compared with the sham group,the left ventricular systolic pressure(LVSP)of rats in each PCB2 intervention group decreased gradually(P<0.05),while the left ventricular enddiastolic pressure(LVEDP),+dp/dtmax and-dp/dtmax increased gradually(P<0.05).In each PCB2 intervention group,myocardial tissue cells showed different degrees of pathological improvement,and the CAS value of myocardial cells gradually decreased(P<0.05),while the expression levels of ANP,BNP,beta-MHC,collagen I,collagen Ⅲ and CTGF genes in cardiomyocytes decreased gradually(P<0.05).The apoptotic rate of cardiomyocytes in the PCB2 intervention groups decreased gradually(P<0.05);the concentration levels of myocardial related inflammatory factors(VCAM-1,MCP-1,ICAM-1,TNF-αand IL-6)in the peripheral blood of rats in the PCB2 intervention groups all gradually decreased(P<0.05)and were similar to those in the CAP action group.In conclusion,PCB2 can significantly improve ventricular remodeling and myocardial function after acute myocardial infarction by inhibiting cardiomyocyte hypertrophy,fibrosis and apoptosis,as well as inhibiting myocardial related inflammatory factors.