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氧化膳食脂质可诱导绝经后大鼠的血管炎症和动脉粥样硬化形成:雌二醇和选定的降脂药物可恢复体内血管健康。

Oxidized dietary lipids induce vascular inflammation and atherogenesis in post-menopausal rats: estradiol and selected antihyperlipidemic drugs restore vascular health in vivo.

机构信息

School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA, 71209, USA.

Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, University of Ilorin, Ilorin, Kwara-State, Nigeria.

出版信息

Lipids Health Dis. 2023 Jul 26;22(1):107. doi: 10.1186/s12944-023-01818-y.

DOI:10.1186/s12944-023-01818-y
PMID:37495992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10369757/
Abstract

BACKGROUND

Thermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when eaten. Consumption of thermoxidized oil in post-menopausal conditions where the estrogen level is low contributes to cardiovascular disease. This study evaluates the role of estradiol and antihyperlipidemic agents (AHD) in restoring the vascular health of ovariectomized (OVX) rats fed with thermoxidized palm oil (TPO) and thermoxidized soya oil (TSO) diets.

METHOD

A total of 10 groups of rats (n = 6) were set up for the experiment. Group I (normal control) rats were sham handled while other groups were OVX to bring about estrogen deficient post-menopausal state. Group II (OVX only) was not treated and received normal rat chow. Groups III-X were fed with either TPO or TSO diet for 12 weeks and treated with estradiol (ETD) 0.2 mg/kg/day, atorvastatin (ATV) 10 mg/kg/day, and a fixed-dose combination of ezetimibe and ATV (EZE 3 mg/kg/day + ATV 10 mg/kg/day).

RESULTS

Pro-atherogenic lipids levels were significantly elevated in untreated TSO and TPO groups compared to OVX and sham, resulting in increased atherogenic and Coronary-risk indices. Treatment with Estradiol and AHDs significantly reduced the total cholesterol, triglycerides, low-density lipoprotein cholesterol as well as AI and CRI compared to untreated TSO and TPO groups, whereas TSO and TPO groups showed significant elevation in these parameters compared to Group I values. Moreover, aortic TNF-α levels were extremely elevated in the untreated TSO and TPO compared to Group I. TNF-α levels were significantly reduced in rats treated with AHDs and ETD. Localized oxidative stress was indicated in the aortic tissues of TSO and TPO-fed OVX rats by increased malondialdehyde and decreased glutathione, catalase, and superoxide dismutase levels. This contributed to a depletion in aortic nitric oxide. AHDs and ETD replenished the nitric oxide levels significantly. Histological evaluation of the aorta of TSO and TPO rats revealed increased peri-adventitia fat, aortic medial hypertrophy, and aortic recanalization. These pathologic changes were less seen in AHDs and ETD rats.

CONCLUSION

This study suggests that ETD and AHDs profoundly attenuate oxidized lipid-induced vascular inflammation and atherogenesis through oxidative-stress reduction and inhibition of TNF-α signaling.

摘要

背景

食用油在深度油炸过程中发生热氧化,会产生多种氧化产物,这些产物在食用时会促进脂质过氧化和 ROS 产生。在雌激素水平较低的绝经后情况下,食用热氧化油会导致心血管疾病。本研究评估了雌二醇和降脂药(AHD)在恢复喂食热氧化棕榈油(TPO)和热氧化大豆油(TSO)饮食的去卵巢(OVX)大鼠血管健康方面的作用。

方法

共设置 10 组大鼠(n=6)进行实验。第 I 组(正常对照组)大鼠接受假手术处理,而其他组大鼠接受去卵巢手术以造成雌激素缺乏的绝经后状态。第 II 组(仅去卵巢)未进行任何处理,接受普通大鼠饲料。第 III-X 组大鼠分别喂食 TPO 或 TSO 饮食 12 周,并每天给予雌二醇(ETD)0.2mg/kg、阿托伐他汀(ATV)10mg/kg 和依泽替米贝和 ATV 的固定剂量组合(EZE 3mg/kg/day+ATV 10mg/kg/day)。

结果

未经治疗的 TSO 和 TPO 组的促动脉粥样硬化脂质水平明显升高,与 OVX 和假手术组相比,导致动脉粥样硬化和冠状动脉风险指数增加。与未经治疗的 TSO 和 TPO 组相比,雌二醇和 AHD 治疗显著降低了总胆固醇、甘油三酯、低密度脂蛋白胆固醇以及 AI 和 CRI,而 TSO 和 TPO 组与第 I 组相比,这些参数显著升高。此外,未经治疗的 TSO 和 TPO 组大鼠的主动脉 TNF-α 水平极高。用 AHD 和 ETD 治疗的大鼠 TNF-α 水平显著降低。在 TSO 和 TPO 喂养的 OVX 大鼠的主动脉组织中,丙二醛增加,谷胱甘肽、过氧化氢酶和超氧化物歧化酶水平降低,表明局部氧化应激增加,导致主动脉一氧化氮耗竭。AHD 和 ETD 显著补充了一氧化氮水平。对 TSO 和 TPO 大鼠的主动脉进行组织学评估显示,外膜下脂肪增加、主动脉中层肥大和主动脉再通。这些病理变化在 AHD 和 ETD 大鼠中较少见。

结论

本研究表明,雌二醇和 AHD 通过降低氧化应激和抑制 TNF-α 信号转导,显著减轻氧化脂质诱导的血管炎症和动脉粥样硬化形成。

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