摘要
目的探究速效救心丸对冠心病大鼠的保护作用,初步探究其可能作用机制。方法将40只SD大鼠分为健康组、单纯模型组、速效救心丸组、缺氧诱导因子-1α(HIF-1α)激活剂奥替普拉(Oltipraz)组、速效救心丸+奥替普拉组,每组10只大鼠。对大鼠心电图ST段、T波变化进行检测,采用酶法测定一氧化氮及血脂指标总胆固醇、三酰甘油、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)水平,酶联免疫吸附试验(ELISA)检测大鼠肿瘤坏死因子α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)、细胞间黏附分子-1(ICAM-1)、内皮素-1(ET-1)、前列环素I2(PGI2)水平,HE染色观察心肌组织病理形态学变化情况;DNA断裂的原位末端标记法(TUNEL法)检测心肌组织细胞凋亡情况;蛋白质印迹法检测心肌组织中HIF-1α、Bcl2/腺病毒E1B相互作用蛋白3(BNIP3)、B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、半胱氮酸天冬氨酸蛋白酶-3(caspase-3)蛋白表达。结果与健康组相比,单纯模型组ST段(0.36±0.05)mV、T波(0.26±0.05)mV升高,三酰甘油(1.08±0.14)mmol/L、总胆固醇升高,HDL(0.59±0.05)mmol/L降低,TNF-α(38.27±1.36)pg/mL、ET-1(11.63±1.84)ng/L升高,一氧化氮(28.58±1.53)μmol/L降低,心肌组织细胞凋亡率(46.72±4.37)%升高,HIF-1α(1.12±0.15)、caspase-3(0.54±0.05)蛋白表达升高,Bcl-2(0.36±0.05)蛋白表达降低(P<0.05)。速效救心丸组ST段(0.23±0.04)mV、T波(0.15±0.04)mV、三酰甘油(0.85±0.07)mmol/L、TNF-α(24.69±1.53)pg/mL、ET-1(7.18±1.57)ng/L、细胞凋亡率(15.66±3.51)%、HIF-1α(0.49±0.06)、caspase-3(0.42±0.04)蛋白表达低于单纯模型组,一氧化氮(36.43±1.65)μmol/L、Bcl-2(0.67±0.07)高于单纯模型组(P<0.05)。奥替普拉组ST段(0.41±0.05)mV、T波(0.35±0.03)mV、三酰甘油(1.27±0.12)mmol/L、TNF-α(43.42±1.59)pg/mL、ET-1(12.76±1.45)ng/L、细胞凋亡率(62.88±8.35)%、HIF-1α(1.37±0.26)、caspase-3(0.91±0.09)蛋白表达高于单纯模型组,一氧化氮(23.52±1.84)μmol/L、Bcl-2(0.25±0.04)低于单纯模型组(P<0.05)。速效救心丸+奥替普拉组ST段(0.34±0.06)mV、T波(0.24±0.05)mV、三酰甘油(1.06±0.13)mmol/L、总胆固醇、TNF-α(35.23±1.65)pg/mL、ET-1(11.24±1.73)ng/L、细胞凋亡率(42.76±5.16)%、HIF-1α(1.06±0.17)、caspase-3(0.52±0.06)蛋白表达低于奥替普拉组,一氧化氮(27.24±1.32)μmol/L、Bcl-2(0.38±0.06)高于奥替普拉组(P<0.05)。结论速效救心丸可改善冠心病大鼠血脂、内皮功能,降低机体炎症反应,其可能是通过抑制HIF-1α/BNIP3通路、降低心肌细胞凋亡实现的。
Objective To explore the protective effect of Suxiao Jiuxin pills on rats with coronary heart disease and its possible mechanism.Methods Forty SD rats were assigned into Healthy group,model group,Suxiao Jiuxin pills group,HIF-1αactivator group(Oltipraz),Suxiao Jiuxin pills+Oltipraz group,with 10 rats in each group.The changes of ST segment of electrocardiogram in rats were detected,the levels of nitric oxide,total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL)and low density lipoprotein(LDL)were determined by enzymatic method,the levels of tumor necrosis factor alpha(TNF-α),monocyte chemoattractant protein(MCP-1),intercellular adhesion molecule-1(ICAM-1),endothelin-1(ET-1),and prostacyclin(PGI2)were detected by enzyme-linked immunosorbent assay(ELISA).HE staining was used to observe the pathomorphologic changes of myocardium,the apoptosis of myocardial cells was detected by Tunel method,and the expressions of HIF-1α,BNIP3,Bcl-2,Bax and caspase-3 proteins in myocardium were detected by Western blotting.Results Compared with Healthy group,ST segment[(0.36±0.05)mV] and T wave[(0.26±0.05)mV]increased,TG[(1.08±0.14)mmol/L]and TC increased,HDL[(0.59±0.05)mmol/L]decreased,TNF-α[(38.27±1.36)pg/mL],ET-1[(11.63±1.84)ng/L]increased,NO[(28.58±1.53)μmol/L]decreased,apoptotic rate of myocardial cells[(46.72±4.37)%]increased,expressions of HIF-1α[(1.12±0.15)],caspase-3 proteins[(0.54±0.05)]increased and expression of Bcl-2 protein[(0.36±0.05)]decreased in Model group(P<0.05).The ST segment[(0.23±0.04)mV],T wave[(0.15±0.04)mV],TG[(0.85±0.07)mmol/L],TNF-α[(24.69±1.53)pg/mL],ET-1[(7.18±1.57)ng/L],apoptotic rate[(15.66±3.51)%],HIF-1α[(0.49±0.06)],Caspase-3 proteins[(0.42±0.04)]expressions in Suxiao Jiuxin pills group were lower than those in model group,while the expressions of NO[(36.43±1.65)μmol/L]and Bcl-2[(0.67±0.07)]were higher than those in model group(P<0.05).The ST segment[(0.41±0.05)mV],T wave[(0.35±0.03)mV],TG[(1.27±0.12)mmol/L],TNF-α[(43.42±1.59)pg/mL],ET-1[(12.76±1.45)ng/L],apoptotic rate[(62.88±8.35)%],HIF-1α[(1.37±0.26)],caspase-3 proteins[(0.91±0.09)]expressions in Oltipraz group were higher than those in model group,while the expressions of NO[(23.52±1.84)μmol/L]and Bcl-2[(0.25±0.04)]were lower than those in model group(P<0.05).The ST segment[(0.34±0.06)mV],T wave[(0.24±0.05)mV],TG[(1.06±0.13)mmol/L],total cholesterol,TNF-α[(35.23±1.65)pg/mL],ET-1[(11.24±1.73)ng/L],apoptotic rate[(42.76±5.16)%],HIF-1α[(1.06±0.17)],caspase-3 proteins[(0.52±0.06)]expressions in Suxiao Jiuxin pills+Oltipraz group were lower than those in Oltipraz group,while NO[(27.24±1.32)μmol/L],Bcl-2[(0.38±0.06)]in Suxiao Jiuxi pills+Oltipraz group were higher than those in Oltipraz group(P<0.05).Conclusion Suxiao Jiuxin pills can improve blood lipid and endothelial function and reduce inflammatory reaction in rats with coronary heart disease,which may be achieved by inhibiting HIF-1α/BNIP3 pathway and reducing cardiomyocyte apoptosis.
作者
郭坤
金辉
吴留广
GUO Kun;JIN Hui;WU Liuguang(Department of Cardiovascular Surgery,Zhoukou Central Hospital,Zhoukou,Henan 466000,China)
出处
《安徽医药》
CAS
2020年第6期1078-1083,I0001,共7页
Anhui Medical and Pharmaceutical Journal
