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橙皮素可预防 Wistar 大鼠因柴油废气颗粒引起的心血管氧化应激和炎症。

Hesperetin protects against diesel exhaust particles-induced cardiovascular oxidative stress and inflammation in Wistar rats.

机构信息

Bioinformatics and Molecular Biology Unit, Department of Biochemistry, School of Sciences, Federal University of Technology, Akure, P.M.B. 704, Akure, Ondo-State, Nigeria.

出版信息

Environ Sci Pollut Res Int. 2022 Jul;29(35):52574-52589. doi: 10.1007/s11356-022-19494-3. Epub 2022 Mar 9.

DOI:10.1007/s11356-022-19494-3
PMID:35262885
Abstract

Air particulate matter exposure has been linked to cardiovascular and atherosclerosis as a result of increase oxidative stress and inflammatory response. This study aims to determine the effect of the use of hesperetin (HESP) as a therapeutic agent to mitigate the cardiovascular oxidative and pro-inflammatory effects of diesel exhaust particles in Wistar rats. DEP was collected from an Iveco cargo engine truck, and n-hexane fraction (hDEP) was obtained. Forty Wistar strains of male albino rats (6 weeks) were divided into 8 groups: control group received DMSO and CMC-Na; other groups received either n-hexane extract of DEP (0.064 or 0.640 mg/kg hDEP) or Standard Reference Material 2975 (0.064 mg/kg hSRM) in the presence or absence of 200 mg/kg HESP. Extracts were administered orally. Serum lipids, lipid peroxidation (LPO), conjugated dienes (CDs), and GSH levels were determined. Also, inflammatory cytokines, PCSK-9, LDL-receptor, and antioxidant genes expression were assessed by RT-PCR in both the heart and aorta. The molecular interaction of targeted proteins with HESP was assessed by the in silico approach. Extracts of DEP caused a significant (p < 0.001) increase in serum lipids but significantly decreased HDL-CHOL. It also increased CDs and MDA levels but decreased GSH levels. In addition, the particulate extracts caused a significant (p < 0.001) increase in pro-inflammatory genes expression in the heart and aorta but significantly decreased IL-10 and LDL-R gene expressions. Pre-treatment with hesperetin significantly reversed all these effects. This study shows that hesperetin has the ability to protect against DEP-induced oxidative stress and inflammation in the cardiovascular system.

摘要

空气颗粒物暴露与心血管疾病和动脉粥样硬化有关,这是由于氧化应激和炎症反应增加的结果。本研究旨在确定使用桔皮素(HESP)作为治疗剂来减轻柴油机排气颗粒对 Wistar 大鼠心血管氧化和促炎作用的效果。DEP 从 Iveco 货车发动机中收集,得到正己烷馏分(hDEP)。将 40 只雄性白化 Wistar 大鼠(6 周龄)分为 8 组:对照组给予 DMSO 和 CMC-Na;其他组分别给予 DEP 的正己烷提取物(0.064 或 0.640mg/kg hDEP)或标准参考物质 2975(0.064mg/kg hSRM),同时给予或不给予 200mg/kg HESP。提取物经口给予。测定血清脂质、脂质过氧化(LPO)、共轭二烯(CDs)和 GSH 水平。还通过 RT-PCR 评估心脏和主动脉中炎性细胞因子、PCSK-9、LDL 受体和抗氧化基因的表达。通过计算机模拟方法评估靶向蛋白与 HESP 的分子相互作用。DEP 提取物导致血清脂质显著增加(p<0.001),但高密度脂蛋白胆固醇显著降低。它还增加了 CDs 和 MDA 水平,但降低了 GSH 水平。此外,颗粒提取物导致心脏和主动脉中促炎基因表达显著增加(p<0.001),但 IL-10 和 LDL-R 基因表达显著降低。桔皮素预处理显著逆转了所有这些作用。本研究表明,桔皮素具有保护心血管系统免受 DEP 诱导的氧化应激和炎症的能力。

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