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银纳米颗粒对异丙肾上腺素诱导的大鼠心肌梗死的保护作用。

Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats.

作者信息

Arozal Wawaimuli, Monayo Edwina Rogayah, Barinda Agian Jeffilano, Perkasa Dian Pribadi, Soetikno Vivian, Nafrialdi Nafrialdi, Louisa Melva

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

出版信息

Front Med (Lausanne). 2022 Aug 25;9:867497. doi: 10.3389/fmed.2022.867497. eCollection 2022.

Abstract

BACKGROUND

Silver nanoparticles (AgNPs) are widely used in the medical field, including cardiovascular. However, limited research has investigated the effect of AgNPs on the protection of myocardial infarction (MI).

OBJECTIVES

Isoproterenol (Iso)-induced MI and the cardiac protection offered by AgNPs were investigated in the present study. Additionally, we characterized the profile of Ag in the form of nanoparticles.

METHODS

Twenty-four male Wistar rats were randomly divided into four groups as follows: normal, Iso, Iso + AgNO, and Iso + AgNP groups. AgNPs and silver ion (AgNO) were administered intraperitoneally at 2.5 mg/kg BW for 14 days. Iso induction was performed using two doses of 85 mg/kg BW given subcutaneously on days 13 and 14. Blood and cardiac tissue samples were taken 24 h after the last dose of Iso and checked for Creatine Kinase-MB (CK-MB), lactate dehydrogenase in plasma along with oxidative stress parameters, mitochondria biogenesis markers, and inflammation representative genes in cardiac tissue. Additionally, we analyzed the histopathological features in cardiac tissue.

RESULTS

The silver was confirmed in the form of nanoparticles by its size at intervals of 8.72-37.84 nm. Both AgNO and AgNPs showed similar cardioprotective effects, as shown by the decrease in biochemical markers of cardiac toxicity, namely, CK-MB. Additionally, AgNPs group have better efficacy compared with AgNO group in ameliorating Iso-mediated oxidative stress production, as evidenced by the significant decrease in malondialdehyde level and increased superoxide dismutase activity ( < 0.0001 and < 0.01, respectively) in cardiac tissue compared with the Iso group. Mechanistically, AgNPs, but not AgNO, enhanced the expression levels of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha in post-MI heart and reduced the protein expression of nuclear factor-kappa B (NF-κB) assessed by western blot analysis. Furthermore, these results were confirmed with the histopathological evaluation of cardiac tissue. Nevertheless, pretreatment with either AgNO or AgNPs improved the aspartate aminotransferase level.

CONCLUSION

These results suggested that AgNPs have more superior cardioprotective effect compared with AgNO against Iso-induced MI, at least in part through amelioration of NF-κB expression level induced by oxidative stress overproduction.

摘要

背景

银纳米颗粒(AgNPs)广泛应用于医学领域,包括心血管领域。然而,关于AgNPs对心肌梗死(MI)保护作用的研究有限。

目的

本研究调查异丙肾上腺素(Iso)诱导的MI以及AgNPs提供的心脏保护作用。此外,我们对纳米颗粒形式的银的特征进行了表征。

方法

将24只雄性Wistar大鼠随机分为四组:正常组、Iso组、Iso + AgNO组和Iso + AgNP组。AgNPs和银离子(AgNO)以2.5 mg/kg体重的剂量腹腔注射,持续14天。在第13天和第14天,皮下注射两剂85 mg/kg体重的剂量进行Iso诱导。在最后一剂Iso给药24小时后采集血液和心脏组织样本,检测血浆中的肌酸激酶同工酶(CK-MB)、乳酸脱氢酶以及氧化应激参数、线粒体生物发生标志物和心脏组织中的炎症代表性基因。此外,我们分析了心脏组织的组织病理学特征。

结果

通过其8.72 - 37.84 nm的粒径间隔证实银以纳米颗粒形式存在。AgNO和AgNPs均显示出相似的心脏保护作用,表现为心脏毒性生化标志物CK-MB的降低。此外,与Iso组相比,AgNPs组在改善Iso介导的氧化应激产生方面比AgNO组具有更好的效果,心脏组织中丙二醛水平显著降低和超氧化物歧化酶活性增加(分别为<0.0001和<0.01)证明了这一点。从机制上讲,AgNPs而非AgNO增强了MI后心脏中线粒体转录因子A和过氧化物酶体增殖物激活受体γ共激活因子1α的表达水平,并通过蛋白质印迹分析降低了核因子κB(NF-κB)的蛋白表达。此外,这些结果通过心脏组织的组织病理学评估得到证实。然而,用AgNO或AgNPs预处理均可改善天冬氨酸转氨酶水平。

结论

这些结果表明,与AgNO相比,AgNPs对Iso诱导的MI具有更优越的心脏保护作用,至少部分是通过改善氧化应激过度产生诱导的NF-κB表达水平实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1682/9454814/5b5191a42aa1/fmed-09-867497-g001.jpg

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