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一种新型唾液糖肽通过下调 FXR/FGF15 和 TLR4/TGF-β/Smad 通路预防 CCl 诱导的肝纤维化。

A Novel Sialoglycopeptide from Eggs Prevents Liver Fibrosis Induced by CCl via Downregulating FXR/FGF15 and TLR4/TGF-β/Smad Pathways.

机构信息

College of Food Science and Engineering, Ocean University of China, Qingdao, Shangdong 266003, China.

Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, Shandong Province 266237, P.R. China.

出版信息

J Agric Food Chem. 2021 Nov 10;69(44):13093-13101. doi: 10.1021/acs.jafc.1c05411. Epub 2021 Oct 29.

Abstract

Liver fibrosis plays a critical role in liver disease progression. A sialoglycopeptide from the eggs (Gm-SGPP) was identified having a 7000 Da molecular weight with a core pentasaccharide structure and osteogenesis activity. However, whether Gm-SGPP is beneficial to liver fibrosis remains unknown. In this study, mice with liver fibrosis were intraperitoneally injected with 2.5% CCl (10 mL/kg) and orally administered with Gm-SGPP (500 mg/kg) for 30 days. Results showed that Gm-SGPP alleviated oxidative liver damage and lipid metabolism disorder and reduced hepatocyte necrosis and lipid droplet accumulation. Notably, we found that Gm-SGPP increased the number and changed the composition of bile acids via increasing cholesterol 7a-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) expression, which caused inhibition of ileum farnesoid X receptor (FXR) expression and accelerated the cholesterol conversion. Cholesterol accumulation is a risk factor for liver fibrosis. Masson staining showed that Gm-SGPP significantly reduced the degree of collagen deposition. Western blotting further suggested that Gm-SGPP downregulated the key gene of the toll-like receptor 4 (TLR4)-mediated transforming growth factor-β (TGF-β)/Smad pathway. To our best knowledge, this is the first report that Gm-SGPP prevented liver fibrosis via attenuating cholesterol accumulation. Our present results provide new ideas for the egg's high-value utilization.

摘要

肝纤维化在肝脏疾病的进展中起着关键作用。从鸡蛋中分离出的唾液糖肽(Gm-SGPP)具有 7000Da 的分子量,核心五糖结构和成骨活性。然而,Gm-SGPP 是否对肝纤维化有益尚不清楚。在这项研究中,肝纤维化小鼠通过腹腔注射 2.5% CCl(10mL/kg)并用 Gm-SGPP(500mg/kg)口服给药 30 天。结果表明,Gm-SGPP 减轻了氧化肝损伤和脂质代谢紊乱,减少了肝细胞坏死和脂质滴积聚。值得注意的是,我们发现 Gm-SGPP 通过增加胆固醇 7a-羟化酶(CYP7A1)和固醇 27-羟化酶(CYP27A1)的表达增加了胆汁酸的数量并改变了其组成,从而抑制了回肠法尼醇 X 受体(FXR)的表达并加速了胆固醇转化。胆固醇积累是肝纤维化的一个危险因素。Masson 染色显示 Gm-SGPP 显著降低了胶原沉积程度。Western blot 进一步表明,Gm-SGPP 下调了 Toll 样受体 4(TLR4)介导的转化生长因子-β(TGF-β)/Smad 通路的关键基因。据我们所知,这是首次报道 Gm-SGPP 通过减轻胆固醇积累来预防肝纤维化。我们的研究结果为鸡蛋的高值利用提供了新的思路。

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