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绿茶儿茶素表没食子儿茶素没食子酸酯通过调节微生物群-肠-肝轴改善硫代乙酰胺诱导的大鼠肝性脑病。

Green Tea Catechin EGCG Ameliorates Thioacetamide-Induced Hepatic Encephalopathy in Rats via Modulation of the Microbiota-Gut-Liver Axis.

作者信息

Zhou Zhengming, Li Ke, Guo Jiankui, Wang Yunfeng, Wei Yaoyao, Duan Juan, Chen Muxi, Shi Lei, Hu Wen

机构信息

Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.

Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.

出版信息

Mol Nutr Food Res. 2023 Apr;67(8):e2200821. doi: 10.1002/mnfr.202200821. Epub 2023 Mar 8.

Abstract

SCOPE

Existing research suggests that (-)-epigallocatechin-3-gallate (EGCG), which is a natural tea catechin active substance, can protect against liver injury. However, its mechanism for hepatic encephalopathy (HE) treatment is still unclear. In this study, the role of EGCG in the amelioration of HE rats and the effect on the microbiota-gut-liver axis are mainly analyzed.

METHODS AND RESULTS

Thioacetamide (TAA) is employed to induce the HE model in rats. The results of open field test show that EGCG restores locomotor activity and exploratory behavior. Histological and biochemical results demonstrate that EGCG ameliorates brain and liver damage, decreases the expression of pro-inflammatory cytokines, and increases the activity of antioxidant enzymes. Meanwhile, EGCG modulates the Nrf2 pathway and TLR4/NF-κB pathway to mitigate TAA-induced oxidative stress and inflammatory responses. Immunohistochemistry reveals protection of the intestinal barrier by EGCG upregulating the expression of occludin and zonula occludens-1. Furthermore, serum levels of ammonia and LPS are reduced. 16S rRNA analysis shows that EGCG treatment increases the abundance of beneficial bacteria (e.g., Bifidobacterium, Lactobacillus, and Limosilactobacillus).

CONCLUSION

The above results reveal that EGCG has anti-oxidative stress and anti-inflammatory effects, and ameliorates the condition through the microbiota-gut-liver axis, with potential for the treatment of HE.

摘要

范围

现有研究表明,(-)-表没食子儿茶素-3-没食子酸酯(EGCG)作为一种天然的茶儿茶素活性物质,能够预防肝损伤。然而,其治疗肝性脑病(HE)的机制仍不清楚。在本研究中,主要分析了EGCG在改善HE大鼠中的作用以及对微生物群-肠-肝轴的影响。

方法与结果

采用硫代乙酰胺(TAA)诱导大鼠HE模型。旷场试验结果表明,EGCG可恢复运动活性和探索行为。组织学和生化结果表明,EGCG可改善脑和肝损伤,降低促炎细胞因子的表达,并提高抗氧化酶的活性。同时,EGCG调节Nrf2途径和TLR4/NF-κB途径,以减轻TAA诱导的氧化应激和炎症反应。免疫组织化学显示,EGCG通过上调闭合蛋白和紧密连接蛋白-1的表达来保护肠道屏障。此外,血清氨和LPS水平降低。16S rRNA分析表明,EGCG处理可增加有益菌(如双歧杆菌、乳酸杆菌和迟缓乳杆菌)的丰度。

结论

上述结果表明,EGCG具有抗氧化应激和抗炎作用,并通过微生物群-肠-肝轴改善病情,具有治疗HE的潜力。

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