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亚麻木脂素通过降低母鼠的反式脂肪酸暴露减轻其子代肾脏的氧化损伤

Amelioration of oxidative kidney damage in offspring by maternal trans-fatty acid exposure in mice by secoisolariciresinol diglucoside.

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Bengbu Medical College, Bengbu Anhui 233030, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Jul 28;48(7):967-978. doi: 10.11817/j.issn.1672-7347.2023.220524.

Abstract

OBJECTIVES

Trans-fatty acids (TFAs), primarily derived from the food industry's production processes, have become a globally recognized public health issue due to the detrimental impact they have on human well-being. Secoisolariciresinol diglucoside (SDG) is a polyphenolic compound derived from flax lignans, possessing antioxidative properties. This study aims to investigate the protective effect of SDG on kidney oxidative damage in offspring of mice caused by maternal exposure to TFA during pregnancy and lactation.

METHODS

A total of 30 c57BL/6 female rats were randomly divided into 5 groups: a control group, a TFA-exposed group, a low-(TFA+LSDG) group, a medium-(TFA+MSDG) group, and a high-(TFA+HSDG) group (=6 in each group). With the exception of the control group, the maternal mice in the remaining 4 groups received a daily oral gavage of TFA at a dosage of 60 mg/(kg·BW) throughout the experimental period. The mothers in the control group were administered physiological saline via oral gavage once daily. Meanwhile, the 3 SDG intervention groups were provided with ad libitum access to SDG feed containing 10 mg/kg (low), 20 mg/kg (medium), and 30 mg/kg (high) of SDG. The female mice were conceived overnight. If the vaginal plug appeared in the next morning, the female mice were conceived and included in the experimental stage until the end of the 21th day lactation period. The body weight and kidney mass of offspring were recorded, and the kidney coefficient was calculated. The kidney was detected by HE staining to observe the histopathological changes, and the level of reactive oxidative species (ROS) was detected by fluorescence probe-dihydroethidium (DHE) staining; the expression levels of total superoxide dismutase (T-SOD) and malondialdehyde (MDA) in renal homogenate were detected, and the expression of nuclear factor E2-related fator2 (Nrf2) and hemeoxygenase-1 (HO-1) protein was analyzed by immunohistochemistry (IHC) staining. The mRNA expressions of and were detected by real-time PCR, and the protein expression of Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), glutathione peroxidase-1 (GPx-1), Nrf2 and HO-1 were detected by Western blotting.

RESULTS

Compared with the control group, the kidney coefficient in the TFA-exposed group was increased, the morphology and structure of kidney tissue was abnormal; the activity of T-SOD enzyme was decreased, and the content of MDA was increased, the level of ROS was increased; the expressions of Cu/Zn-SOD, Mn-SOD, GPx1 protein were decreased, and the mRNA and protein expressions of Nrf2 and HO-1 were decreased, there were all significant difference (all <0.05). Compared with the TFA-exposed group, the ROS levels were reduced, and the T-SOD enzyme activity as well as the protein expression of Cu/Zn-SOD, GPx-1, Mn-SOD, Nrf2 and HO-1 were up-regulated in the low, middle and high dose SDG intervention groups; the kidney coefficient and MDA content were decreased in the middle and high dose SDG groups; the mRNA expression in the high dose SDG group was up-regulated, there were all significant difference (all <0.05).

CONCLUSIONS

Maternal exposure to TFA during pregnancy and lactation can lead to oxidative damage in the kidney of offspring, and the SDG intervention may alleviate TFA-induced oxidative damage by up-regulating the expression of Nrf2 and HO-1 signal pathway.

摘要

目的

反式脂肪酸(TFAs)主要来源于食品工业的生产过程,由于其对人类健康的不利影响,已成为全球公认的公共卫生问题。二氢松柏醇葡萄糖苷(SDG)是一种源自亚麻木质素的多酚化合物,具有抗氧化特性。本研究旨在探讨 SDG 对母体在妊娠和哺乳期暴露于 TFA 时对子代小鼠肾脏氧化损伤的保护作用。

方法

将 30 只 c57BL/6 雌性大鼠随机分为 5 组:对照组、TFA 暴露组、低剂量(TFA+LSDG)组、中剂量(TFA+MSDG)组和高剂量(TFA+HSDG)组(每组 6 只)。除对照组外,其余 4 组母鼠在整个实验期间每天经口灌胃 TFA,剂量为 60mg/(kg·BW)。对照组母鼠每天经口灌胃生理盐水一次。同时,3 个 SDG 干预组给予自由摄入含 SDG 的饲料,SDG 含量分别为 10mg/kg(低)、20mg/kg(中)和 30mg/kg(高)。让母鼠一夜情受孕。如果第二天早上出现阴道塞,则认为母鼠受孕并纳入实验阶段,直到第 21 天哺乳期结束。记录仔鼠的体重和肾脏质量,计算肾脏系数。用 HE 染色法观察肾脏组织病理学变化,用荧光探针二氢乙啶(DHE)染色法检测活性氧(ROS)水平;检测肾匀浆中总超氧化物歧化酶(T-SOD)和丙二醛(MDA)的表达水平,用免疫组织化学(IHC)染色法分析核因子 E2 相关因子 2(Nrf2)和血红素加氧酶-1(HO-1)蛋白的表达。用实时 PCR 检测 、 的 mRNA 表达,用 Western blot 检测 Cu/Zn-超氧化物歧化酶(Cu/Zn-SOD)、Mn-超氧化物歧化酶(Mn-SOD)、谷胱甘肽过氧化物酶-1(GPx-1)、Nrf2 和 HO-1 的蛋白表达。

结果

与对照组相比,TFA 暴露组的肾脏系数增加,肾脏组织形态和结构异常;T-SOD 酶活性降低,MDA 含量增加,ROS 水平升高;Cu/Zn-SOD、Mn-SOD、GPx1 蛋白表达降低,Nrf2 和 HO-1 的 mRNA 和蛋白表达降低,差异均有统计学意义(均<0.05)。与 TFA 暴露组相比,低、中、高剂量 SDG 干预组 ROS 水平降低,T-SOD 酶活性以及 Cu/Zn-SOD、GPx-1、Mn-SOD、Nrf2 和 HO-1 蛋白表达升高;中、高剂量 SDG 组肾脏系数和 MDA 含量降低;高剂量 SDG 组 mRNA 表达上调,差异均有统计学意义(均<0.05)。

结论

母体在妊娠和哺乳期暴露于 TFA 会导致子代肾脏氧化损伤,SDG 干预可能通过上调 Nrf2 和 HO-1 信号通路的表达来减轻 TFA 诱导的氧化损伤。

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