Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi 330045, P. R. China.
Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi 330045, P. R. China.
Poult Sci. 2022 Jan;101(1):101572. doi: 10.1016/j.psj.2021.101572. Epub 2021 Oct 29.
Avian pathogenic Escherichia coli (APEC) is the causative agent of avian colibacillosis. Baicalin (BA) possesses multiple pharmacological effects, but the mechanism underlying its activity in APEC-induced intestinal injury remains unknown. This study aims to investigate the protective effects and possible mechanism of BA against APEC-induced intestinal injury. Sixty 1-day-old chicks were randomly divided into 4 groups: the control group (basal diet), E. coli group (basal diet), BAI10 group (10 mg/kg BA), and BAI20 group (20 mg/kg BA). After pretreatment with BA for 15 d and subsequent induction of APEC infection by pectoralis injection, the ileum was collected and analyzed. The results showed that BA-pretreatment demonstrated an alleviation of chicks in diarrhea rate, mortality, and histopathological changes in intestinal tissues after APEC infection. Additionally, following APEC infection, BA improved the intestinal barrier by elevating zona occludens (ZO)s (ZO-1, 2, 3), Claudins (Claudin1, 2, 3), Occludin, avian β-defensin (AvBD)s (AvBD1, 2, 4), lysozyme (Lyz) mRNA levels and ZO-1, Claudin1, and Occludin protein levels. Besides, the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and the SOD-1 and CAT mRNA levels and SOD-1 protein level were elevated by BA pretreatment. BA pretreatment also decreased the malondialdehyde (MDA) content, heme oxygenase-1 (HO-1) and NADH quinone oxidoreductase 1 (NQO1) mRNA levels, and HO-1 protein level after APEC infection. BA alleviated the APEC-induced inflammatory response, including downregulating the mRNA levels of proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin [IL]-1β, IL-6, IL-8) and upregulating the mRNA levels of anti-inflammatory cytokines (IL-4, IL-10, IL-13, transforming growth factor-β [TGF-β]). Furthermore, BA decreased the mRNA and protein levels of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and nuclear factor kappa-B (NF-κB) as well as the expression of the phosphorylated forms of these proteins after APEC infection. Collectively, our findings indicate that BA exerts a protective effect against APEC-induced intestinal injury in chicks by inhibiting the PI3K/AKT-mediated NF-κB pathway, suggesting that BA may be a potential therapeutic approach for avian colibacillosis.
禽致病性大肠杆菌（APEC）是禽大肠杆菌病的病原体。黄芩苷（BA）具有多种药理作用，但其在 APEC 诱导的肠道损伤中的作用机制尚不清楚。本研究旨在探讨 BA 对 APEC 诱导的肠道损伤的保护作用及可能机制。
将 60 只 1 日龄雏鸡随机分为 4 组：对照组（基础日粮）、大肠杆菌组（基础日粮）、BAI10 组（10mg/kg BA）和 BAI20 组（20mg/kg BA）。BA 预处理 15d 后，通过胸肌注射诱导 APEC 感染，采集回肠进行分析。结果显示，BA 预处理可减轻 APEC 感染后雏鸡腹泻率、死亡率和肠道组织的组织病理学变化。此外，APEC 感染后，BA 通过提高紧密连接蛋白（ZO）（ZO-1、2、3）、Claudin（Claudin1、2、3）、Occludin、禽β-防御素（AvBD）（AvBD1、2、4）、溶菌酶（Lyz）mRNA 水平和 ZO-1、Claudin1 和 Occludin 蛋白水平来改善肠道屏障。此外，BA 预处理还可提高总超氧化物歧化酶（T-SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性，以及 SOD-1 和 CAT mRNA 水平和 SOD-1 蛋白水平。BA 预处理还可降低丙二醛（MDA）含量、血红素加氧酶-1（HO-1）和烟酰胺腺嘌呤二核苷酸磷酸氧化还原酶 1（NQO1）mRNA 水平和 HO-1 蛋白水平。BA 还减轻了 APEC 诱导的炎症反应，包括下调促炎细胞因子（肿瘤坏死因子-α（TNF-α）、白细胞介素 [IL]-1β、IL-6、IL-8）的 mRNA 水平和上调抗炎细胞因子（IL-4、IL-10、IL-13、转化生长因子-β[ TGF-β]）的 mRNA 水平。此外，BA 还降低了 APEC 感染后磷脂酰肌醇 3 激酶（PI3K）、蛋白激酶 B（AKT）和核因子 kappa-B（NF-κB）的 mRNA 和蛋白水平以及这些蛋白的磷酸化形式的表达。
综上所述，本研究结果表明，BA 通过抑制 PI3K/AKT 介导的 NF-κB 通路发挥抗 APEC 诱导的雏鸡肠道损伤作用，提示 BA 可能成为禽大肠杆菌病的潜在治疗方法。
