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丁香酸和白藜芦醇联合通过抑制 NF-κB 和 TNF-α 通路对异丙肾上腺素诱导的大鼠心脏毒性的心脏保护作用。

Combined cardio-protective ability of syringic acid and resveratrol against isoproterenol induced cardio-toxicity in rats via attenuating NF-kB and TNF-α pathways.

机构信息

Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, Andhra Pradesh, India.

Central Laboratory, Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

出版信息

Sci Rep. 2020 Feb 25;10(1):3426. doi: 10.1038/s41598-020-59925-0.

DOI:10.1038/s41598-020-59925-0
PMID:32099011
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7042357/
Abstract

The study was conducted to evaluate the cardio-protective activity of combination (COMB) of syringic acid (SA) and resveratrol (RV) against isoproterenol (ISO) induced cardio-toxicity in rats. Rats were pre-treated orally with SA (50 mg/kg), RV (50 mg/kg) and combination of SA (25 mg/kg) and RV (25 mg/kg) along with positive control gallic acid (50 mg/kg) for 30 days. The effects of ISO on cardiac markers, lipid profile and lipid peroxidation marker, anti-oxidant enzymes and m-RNA expression of nuclear factor-kappa B (NF-kB) and tumor necrosis factor-α (TNF-α) were observed along with histopathological observations of simple and transmission electron microscopes (TEM). Serum creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and alkaline phosphatase were significantly increased while cardiac tissue CK-MB, LDH, superoxide dismutase and catalase were significantly decreased in ISO administered rats, which also exhibited a significant increase in total cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and thiobarbutyric acid reactive substances and significant decrease in high density lipoprotein cholesterol in serum and heart. The m-RNA levels of inflammatory markers NF-kB and TNF-α were significantly increased in ISO treated rats. COMB Pre-treatment significantly reversed the ISO actions. Histopathological studies of simple and TEM were also co-related with the above biochemical parameters. Docking studies with NF-kB were also performed. Evidence has shown for the first time in this approach that COMB pre-treatment ameliorated ISO induced cardio-toxicity in rats and revealed cardio-protection.

摘要

本研究旨在评估丁香酸(SA)和白藜芦醇(RV)联合(COMB)对异丙肾上腺素(ISO)诱导的大鼠心脏毒性的心脏保护活性。大鼠预先经口给予 SA(50mg/kg)、RV(50mg/kg)和 SA(25mg/kg)和 RV(25mg/kg)联合用药(COMB)以及阳性对照没食子酸(50mg/kg),连续 30 天。观察 ISO 对心脏标志物、脂质谱和脂质过氧化标志物、抗氧化酶以及核因子-κB(NF-κB)和肿瘤坏死因子-α(TNF-α)的 m-RNA 表达的影响,并进行简单和透射电子显微镜(TEM)的组织病理学观察。血清肌酸激酶同工酶-MB(CK-MB)、乳酸脱氢酶(LDH)和碱性磷酸酶显著升高,而 ISO 给药大鼠心脏组织 CK-MB、LDH、超氧化物歧化酶和过氧化氢酶显著降低,血清和心脏总胆固醇、甘油三酯、低密度脂蛋白胆固醇、极低密度脂蛋白胆固醇和硫代巴比妥酸反应物显著增加,高密度脂蛋白胆固醇显著降低。ISO 处理大鼠炎症标志物 NF-κB 和 TNF-α 的 m-RNA 水平显著升高。COMB 预处理显著逆转了 ISO 的作用。简单和 TEM 的组织病理学研究也与上述生化参数相关。还对 NF-kB 进行了对接研究。首次在本研究中证明,COMB 预处理可改善 ISO 诱导的大鼠心脏毒性,并显示出心脏保护作用。

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