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苦荞槲皮素通过Toll样受体4或核因子κB途径对高脂饮食大鼠脂质代谢和肠道菌群的调节作用机制

Mechanism of action of buckwheat quercetin in regulating lipid metabolism and intestinal flora via Toll-like receptor 4 or nuclear factor κB pathway in rats on a high-fat diet.

作者信息

Xie Linlin, Chi Xiaoxing, Wang Helin, Dai Anna, Dong Jiaping, Liu Shufan, Zhang Dongjie

机构信息

Department of Food Science and Engineering, College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang Province, China.

Department of Food Science and Engineering, College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang Province, China; National Coarse Cereals Engineering Research Center, Daqing, Heilongjiang Province, China.

出版信息

Nutrition. 2023 Nov;115:112148. doi: 10.1016/j.nut.2023.112148. Epub 2023 Jul 1.

Abstract

OBJECTIVES

Buckwheat quercetin (QUE) was used as a dietary supplement to investigate the mechanism of QUE on the regulation of lipid metabolism and intestinal flora in hyperlipidemic rats.

METHODS

Here, using a high-fat diet-induced hyperlipidemia model, the intervention was carried out by gavage of QUE at doses of 50, 100, and 200 mg/kg. Serum lipid levels, liver biochemical parameters, and histopathologic changes in the liver and intestinal microorganisms were measured in rats by enzyme-linked immunosorbent assay, hematoxylin-eosin, and high-throughput sequencing, respectively.

RESULTS

Our results found that QUE, at a dose of 200 mg/kg, significantly reduced body weight, liver index, and lipid levels in rats (P < 0.05); improved hepatic oxidative stress; and repaired liver injury. In addition, the upregulation of beneficial bacteria, such as christensenellaceae and Bifidobacterium, in the organism increased the content of short-chain fatty acids, thus interfering with intestinal pH and improving the intestinal environment, while downregulating the relative abundance of Proteobacteria and Eubacterium_coprostanoligenes_group, and regulating the overproduction of butyrate. The real-time fluorescence quantitative polymerase chain reaction results found that QUE inhibited the expression of Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA content and blocked the activation of the TLR4/NF-κB signaling pathway, thus affecting the downregulation of lipid levels and restoring intestinal homeostasis.

CONCLUSIONS

A QUE dose of 200 mg/kg may improve lipid levels and the composition of intestinal flora through the TLR4/NF-κB pathway, suggesting that proteobacteria and christensenellaceae abundance changes may be biomarkers of potential diseases.

摘要

目的

以荞麦槲皮素(QUE)作为膳食补充剂,研究QUE对高脂血症大鼠脂质代谢及肠道菌群调节作用的机制。

方法

在此,采用高脂饮食诱导的高脂血症模型,通过灌胃给予50、100和200 mg/kg剂量的QUE进行干预。分别采用酶联免疫吸附测定法、苏木精-伊红染色法和高通量测序法检测大鼠的血脂水平、肝脏生化参数以及肝脏和肠道微生物的组织病理学变化。

结果

我们的研究结果发现,200 mg/kg剂量的QUE可显著降低大鼠体重、肝脏指数和血脂水平(P<0.05);改善肝脏氧化应激;修复肝脏损伤。此外,机体中有益菌如克里斯滕森菌科和双歧杆菌的上调增加了短链脂肪酸的含量,从而干扰肠道pH值并改善肠道环境,同时下调变形菌门和产粪甾醇真杆菌属组的相对丰度,并调节丁酸的过量产生。实时荧光定量聚合酶链反应结果发现,QUE抑制Toll样受体4(TLR4)和核因子κB(NF-κB)mRNA含量的表达,阻断TLR4/NF-κB信号通路的激活,从而影响血脂水平的下调并恢复肠道稳态。

结论

200 mg/kg剂量的QUE可能通过TLR4/NF-κB途径改善血脂水平和肠道菌群组成,提示变形菌门和克里斯滕森菌科丰度变化可能是潜在疾病的生物标志物。

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