机构地区:[1]长沙医学院第一附属医院超声科,湖南长沙410219 [2]长沙医学院第一附属医院心内科,湖南长沙410219 [3]长沙医学院第一附属医院中西医结合科,湖南长沙410219
出 处:《临床和实验医学杂志》2019年第20期2157-2160,共4页Journal of Clinical and Experimental Medicine
基 金:湖南省教育厅科学研究项目(编号:16C0165)
摘 要:目的研究葡萄籽原花青素提取物(GSPE)对心肌梗死大鼠心功能的影响及其可能机制。方法取48只SD大鼠,其中40只用于建立心肌梗死大鼠模型,并随机分为模型组、GSPE低剂量组、GSPE中剂量组、GSPE高剂量组及BSI-201组,每组各8只,余8只大鼠为假手术对照组。模型组与对照组均给予等量生理盐水灌胃,GSPE低剂量组采用100 mg/ml GSPE进行灌胃给药,GSPE中剂量组采用200 mg/ml GSPE进行灌胃给药,GSPE高剂量组给予400 mg/ml GSPE进行灌胃给药,BSI-201组采用多聚腺苷酸二磷酸核糖聚合酶-1(PARP-1)抑制剂BSI-201 120 mol/L进行灌胃给药,1次/d,持续1个月。采用彩色多普勒超声心动图评估各组大鼠心功能状况,记录心率(HR)、左心室舒张末压(LVEDP)及左心室收缩压(LVSP)。通过苏木精-伊红染色评估各组大鼠心肌组织病理学改变状况,采用TUNEL法对大鼠心肌细胞凋亡情况进行检测,并用蛋白免疫印迹法检测大鼠心肌组织中PAR、切割的Caspase-3(c-Caspase-3)、Bcl-2及Bax蛋白的表达水平。结果相比对照组,模型组大鼠LVSP明显下降,HR、LVEDP及细胞凋亡率明显升高(P<0.05),心肌纤维排列不一,心肌细胞破碎,出现大量炎性细胞浸润;心肌组织中Bcl-2蛋白表达水平显著下降,PAR、c-Caspase-3及Bax蛋白的表达水平明显升高(P<0.05)。相比模型组,GSPE低、中、高剂量组和BSI-201组大鼠LVSP明显升高,HR、LVEDP及细胞凋亡率显著下降(P<0.05),心肌组织病理损伤程度明显减轻;心肌组织中Bcl-2蛋白表达水平显著升高,PAR、c-Caspase-3及Bax蛋白的表达水平明显下降(P<0.05),并呈剂量依赖性。结论GSPE可呈剂量依赖性有效改善心肌梗死大鼠心脏功能,其作用机制可能与阻滞PARP-1活化以起到阻滞心肌细胞凋亡的作用密切相关。Objective To study the effect of grape seed proanthocyanidin extract(GSPE)on cardiac function in rats with acute myocardial infarction and its possible mechanism.Methods Forty-eight SD rats were randomly divided into acute myocardial infarction model group,low-dose GSPE group,middle-dose GSPE group,high-dose GSPE group and BSI-201 group,with eight rats in each group,and eight rats were used as sham-operated control group.The model group and the control group were given the same amount of saline by gavage,the low-dose group was given 100 mg/ml GSPE by gavage,the middle-dose group was given 200 mg/ml GSPE by gavage,the high-dose group was given 400 mg/ml GSPE by gavage,and the BSI-201 group was given BSI-120 mol/L,a PARP-1 inhibitor,1 time/day,lasted for one month.Cardiac function was assessed by color Doppler echocardiography.Heart rate(HR),left ventricular end diastolic pressure(LVEDP)and left ventricular systolic pressure(LVSP)were recorded.Myocardial histopathological changes were assessed by hematoxylin-eosin staining.Apoptosis of myocardial cells was detected by TUNEL method.PAR,cleaved Caspase-3(c-Caspase-3),Bcl-2 and Bax protein were detected by Western blot.Results Compared with the control group,LVSP in the model group decreased significantly,HR,LVEDP and apoptotic rate increased significantly(P<0.05),myocardial fibers arranged differently,myocardial cells were broken and a large number of inflammatory cells infiltrated;Bcl-2 protein expression in myocardial tissue decreased significantly,and PAR,c-Caspase-3 and Bax protein expression levels increased significantly(P<0.05).Compared with the model group,the LVSP of rats in low,medium and high dose GSPE group and BSI-201 group increased significantly,the HR,LVEDP and apoptotic rate decreased significantly(P<0.05),the degree of myocardial pathological injury decreased significantly,the expression of Bcl-2 protein in myocardial tissue increased significantly,and the expression levels of PAR,c-Caspase-3 and Bax protein decreased significantly(P<0.05).Conclusio
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