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虾青素通过调节盲肠微生物多样性和 TLR4/MyD88/NF-B 信号通路缓解黄曲霉毒素 A 诱导的小鼠盲肠损伤和炎症。

Astaxanthin Alleviates Ochratoxin A-Induced Cecum Injury and Inflammation in Mice by Regulating the Diversity of Cecal Microbiota and TLR4/MyD88/NF-B Signaling Pathway.

机构信息

Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China.

出版信息

Oxid Med Cell Longev. 2021 Jan 5;2021:8894491. doi: 10.1155/2021/8894491. eCollection 2021.

DOI:10.1155/2021/8894491
PMID:33505592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7806395/
Abstract

Ochratoxin A (OTA) is a common environmental pollutant found in a variety of foods and grains, and excessive OTA consumption causes serious global health effects on animals and humans. Astaxanthin (AST) is a natural carotenoid that has anti-inflammatory, antiapoptotic, immunomodulatory, antitumor, antidiabetes, and other biological activities. The present study is aimed at investigating the effects of AST on OTA-induced cecum injury and its mechanism of action. Eighty C57 mice were randomly divided into four groups, including the control group, OTA group (5 mg/kg body weight), AST group (100 mg/kg body weight), and AST intervention group (100 mg/kg body weight AST+5 mg/kg body weight OTA). It was found that AST decreased the endotoxin content, effectively prevented the shortening of mouse cecum villi, and increased the expression levels of tight junction (TJ) proteins, consisting of occludin, claudin-1, and zonula occludens-1 (ZO-1). AST increased the number of goblet cells, the contents of mucin-2 (MUC2), and defensins (Defa5 and -pD2) significantly, while the expression of mucin-1 (MUC1) decreased significantly. The 16S rRNA sequencing showed that AST affected the richness and diversity of cecum flora, decreased the proportion of lactobacillus, and also decreased the contents of short-chain fatty acids (SCFAs) (acetate and butyrate). In addition, AST significantly decreased the expression of TLR4, MyD88, and p-p65, while increasing the expression of p65. Meanwhile, the expression of inflammatory factors including TNF- and INF- decreased, while the expression of IL-10 increased. In conclusion, AST reduced OTA-induced cecum injury by regulating the cecum barrier function and TLR4/MyD88/NF-B signaling pathway.

摘要

赭曲霉毒素 A(OTA)是一种常见的环境污染物,存在于多种食物和谷物中,过量摄入 OTA 会对动物和人类的健康造成严重的全球性影响。虾青素(AST)是一种天然类胡萝卜素,具有抗炎、抗凋亡、免疫调节、抗肿瘤、抗糖尿病等多种生物学活性。本研究旨在探讨 AST 对 OTA 诱导的盲肠损伤的作用及其作用机制。将 80 只 C57 小鼠随机分为对照组、OTA 组(5mg/kg 体重)、AST 组(100mg/kg 体重)和 AST 干预组(100mg/kg 体重 AST+5mg/kg 体重 OTA)。结果发现,AST 降低了内毒素含量,有效防止了小鼠盲肠绒毛缩短,并增加了紧密连接(TJ)蛋白的表达水平,包括闭合蛋白、Claudin-1 和紧密连接蛋白-1(ZO-1)。AST 增加了杯状细胞的数量,显著增加了粘蛋白-2(MUC2)和防御素(Defa5 和 -pD2)的含量,而粘蛋白-1(MUC1)的表达显著降低。16S rRNA 测序结果显示,AST 影响盲肠菌群的丰富度和多样性,降低了乳酸杆菌的比例,同时降低了短链脂肪酸(SCFAs)(乙酸和丁酸)的含量。此外,AST 显著降低了 TLR4、MyD88 和 p-p65 的表达,同时增加了 p65 的表达。同时,TNF-α和 INF-等炎症因子的表达减少,而 IL-10 的表达增加。综上所述,AST 通过调节盲肠屏障功能和 TLR4/MyD88/NF-B 信号通路减轻 OTA 诱导的盲肠损伤。

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