The protective effect of piperine against isoproterenol-induced inflammation in experimental models of myocardial toxicity.
The protective effect of piperine against isoproterenol-induced inflammation in experimental models of myocardial toxicity.
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DOI：
10.1016/j.ejphar.2020.173524
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发表时间：
2020-08
影响因子：
5
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心肌梗死（MI）最终由于炎性因子和促炎因子的释放而加剧炎症反应。本研究的目的是探讨胡椒碱补充剂对异丙肾上腺素（ISO）诱导的MI炎症反应的保护作用。Masson毛状体染色测定心肌组织结构。免疫组化检测IL-6、TNF-α。RT-PCR检测IL-6、TNF-α、iNOS、eNOS、MMP-2、MMP-9和胶原-III的基因表达。Western印迹法测定HIF-1α、VEGF、Nrf-2、NF-κ B、考克斯-2、p-38、磷酸化p38、ERK-1/2、磷酸化ERK-1/2和胶原蛋白I的表达。在单独接受ISO的大鼠心脏心肌组织中，HIF-1α、VEGF和iNOS表达显著上调，同时eNOS表达下降，而胡椒碱预处理阻止了ISO给药大鼠的这些变化。目前的结果显示，在ISO给药组的心脏组织中，ROS介导的MAPK，即p-p38，p-ERK 1/2的激活。异丙肾上腺素预处理可显著抑制ISO治疗组的上述变化。NF-κB参与调节负责组织修复的基因表达。胡椒碱预处理组可显著降低ISO诱导的NF-κB-p65表达，减轻心肌炎症程度。据报道，与对照组相比，ISO治疗后心脏纤维化显著增加，这是由于羟脯氨酸含量、MMP-2和MMP-9增加以及胶原蛋白-I的上调。与接受ISO注射的组相比，所有这些心脏肥大标志物在“胡椒碱预处理ISO给药组”中均降低。目前的研究结果表明，胡椒碱作为一种营养干预可以防止ISO诱导的MI的心肌炎症。
Myocardial infarction (MI) eventually exacerbates inflammatory response due to the release of inflammatory and pro-inflammatory factors. The aim of this study is to explore the protective efficacy of piperine supplementation against the inflammatory response in isoproterenol (ISO)-induced MI. Masson Trichome staining was executed to determine myocardial tissue architecture. Immunohistochemistry was performed for IL-6, TNF-α. RT-PCR studies were performed to ascertain the gene expression of IL-6, TNF-α, iNOS, eNOS, MMP-2, MMP-9, and collagen-III. Western blotting was performed to determine expression of HIF-1α, VEGF, Nrf-2, NF-ƙB, Cox-2, p-38, phospho-p38, ERK-1/2, phospho-ERK-1/2, and collagen-I. HIF-1α, VEGF, and iNOS expression were significantly upregulated with concomitant decline in eNOS expression in the heart myocardial tissue of rats received ISO alone whereas piperine pretreatment prevented these changes in ISO administered rats. Current results revealed ROS-mediated activation of MAPKs, namely, p-p38, p-ERK1/2 in the heart tissue of ISO administered group. Piperine pretreatment significantly prevented these changes in ISO treated group. NF-κB is involved in the modulation of gene expressions responsible for tissue repair. ISO-induced NF-κB-p65 expression was significantly reduced in the group pretreated with piperine and mitigated extent of myocardial inflammation. A significant increase in cardiac fibrosis upon ISO treatment was reported due to the increased hydroxyproline content, MMP-2 & 9 and upregulation of collagen-I protein compared to control group. All these cardiac hypertrophy markers were decreased in ‘piperine pretreated ISO administered group’ compared to group received ISO injection. Current findings concluded that piperine as a nutritional intervention could prevent inflammation of myocardium in ISO-induced MI.