黄芪甲苷下调PARP-1表达对心肌梗死大鼠的保护作用研究
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Study on Protective Effect of Astragaloside IV Down-Regulating PARP- 1 Expressions on Rats with Myocardial Infarction
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    摘要:

    目的:探讨黄芪甲苷对心肌梗死大鼠的保护作用,并对其作用机制进行初步探索。方法:制备心肌梗死大鼠模型60 只,将其随机分为模型组、黄芪甲苷低、中、高剂量组及硫氮卓酮组,每组12 只,另取12 只SD 大鼠作为假手术组。建模成功后,黄芪甲苷低、中、高剂量组及硫氮卓酮组分别按20.00、40.00、80.00、2.61 mg/(kg·d) 的剂量灌胃相应的药物,假手术组及模型组大鼠以等量的生理盐水灌胃,持续7 d。末次给药结束后24 h,麻醉断头处死大鼠。用三苯基氯化四氮唑(TTC) 染色检测各组大鼠心肌梗死面积;酶联免疫吸附实验(ELISA) 检测各组大鼠血清中磷酸肌酸同工酶(CK-MB)、肌钙蛋白I(cTnI)的水平;超声检测大鼠左心室功能,比较各组大鼠左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左心射血分数(LVEF)、左心室短轴缩短率(FS) 的变化,检测大鼠血液动力学,比较各组左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、左心室内压上升最大速率(+dp/dtmax)、左心室内压下降最大速率(-dp/dtmax);免疫印迹实验(Western blot) 检测各组大鼠心肌组织中多聚腺苷酸-核糖聚合酶1(PARP-1) 蛋白的表达情况。结果:与假手术组比较,模型组大鼠心肌梗死面积、CK-MB、cTnI、LVEDD、LVESD、LVEDP、-dp/dtmax 及PARP-1 蛋白表达均明显升高(P<0.05), LVEF、FS、LVSP、+dp/dtmax 均明显降低(P<0.05);与模型组比较,黄芪甲苷各剂量组及硫氮卓酮组大鼠心肌梗死面积、CK-MB、cTnI、LVEDD、LVESD、LVEDP、-dp/dtmax 及PARP-1 蛋白表达均降低(P<0.05),LVEF、FS、LVSP、+dp/dtmax 均升高(P<0.05),且黄芪甲苷各剂量组呈剂量依赖性(P<0.05)。结论:黄芪甲苷可下调PARP-1 蛋白表达,降低心肌梗死模型大鼠心肌梗死情况,改善大鼠心功能及血流动力学,起到心肌保护作用。

    Abstract:

    Abstract:Objective:To investigate the protective effect of astragaloside IV on rats with myocardial infarction,and to preliminarily explore its mechanism. Methods:A total of 60 model rats with myocardial infarction were prepared and randomly divided into the model group,the astragaloside IV groups with low,medium and high dose respectively and the diltiazem group,with 12 rats in each group;another 12 SD rats were selected as the sham operation group. After successful model establishment,the astragaloside IV groups with low,medium and high dose respectively as well as the diltiazem group were given the corresponding medicines by gavage at doses of 20.00,40.00,80.00 and 2.61 mg/(kg·d) respectively. The sham operation group and the model group were given the same amount of normal saline by gavage. All groups were treated for seven days. At 24 hours after the last administration, the rats were anesthetized and decapitated. In each group, the myocardial infarction areas of rats were detected by triphenyl tetrazolium chloride (TTC) staining;the levels of creatine kinase- MB (CK-MB) and cardiac troponin I (cTnI) in serum were detected by Enzyme Linked Immunosorbent Assay (ELISA);the left ventricular function was detected by ultrasound; the changes of left ventricular end- systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD),left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (FS) were compared; the hemodynamics was detected; the left ventricular systolic pressure (LVSP), left ventricular enddiastolic pressure (LVEDP),+dp/dtmax and -dp/dtmax were compared;the expressions of PARP-1 protein in cardiac tissue of rats were detected by Western blot. Results:When compared with those in the sham operation group,the myocardial infarction areas,CK- MB,cTnI,LVEDD,LVESD,LVEDP,- dp/dtmax and expressions of PARP- 1 protein in the model group were significantly increased (P <0.05) , and the LVEF , FS , LVSP and + dp/dtmax were significantly decreased (P < 0.05); when compared with those in the model group, the myocardial infarction areas, CK- MB, cTnI, LVEDD, LVESD,LVEDP,-dp/dtmax,and expressions of PARP-1 protein in the astragaloside IV groups with different doses and the diltiazem group were decreased(P<0.05), and the LVEF, FS, LVSP, and + dp/dtmax were increased (P<0.05); the astragaloside IV groups with different doses were in a dose- dependent manner(P <0.05). Conclusion:Astragaloside IV can down- regulate the expressions of PARP- 1 protein,reduce the myocardial infarction in model rats as well as improve the heart function and hemodynamics,so as to protect the myocardium.

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周小芳,周思薇.黄芪甲苷下调PARP-1表达对心肌梗死大鼠的保护作用研究[J].新中医,2020,52(14):1-5

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  • 在线发布日期: 2020-07-20
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