禽致病性大肠杆菌(APEC)是鸡大肠杆菌病的病原体。芍药苷,从芍药中提取的天然成分,具有多种药理作用,包括抗炎和免疫调节。然而,其在APEC诱导的鸡急性肺损伤(ALI)中的作用和机制尚不清楚。本研究旨在探讨芍药苷对APEC诱导的ALI的保护作用及其可能机制。从9d大龄开始,灌胃给予芍药苷(25、50和100mg/kg)5d,并在12d大龄时通过腹膜内注射感染APEC。在APEC感染36小时后收集组织用于分析。结果表明,芍药苷明显缓解了症状,提高了感染APEC的鸡的存活率和体重增加,并改善了组织病理学损伤,减少了肺组织中的APEC负荷。此外,芍药苷恢复了APEC感染期间ZO-1,Occludin和Claudin-3的基因表达。此外,芍药苷预处理通过增加DAGL显著影响内源性大麻素系统(ECs),减少MAGL,增加2-AG的分泌。然后,芍药苷显著降低IL-1β的分泌,肺组织中IL-6和TNF-α,并降低CXCL8、CXCL12、CCL1、CCL5和CCL17的mRNA表达。此外,芍药苷显著降低PI3K的磷酸化水平,AKT,P65和IκB。总之,我们发现芍药苷抑制APEC诱导的ALI,其机制可能是通过影响ECs,抑制PI3K/AKT和NF-κB信号通路的激活,为鸡大肠杆菌病的防治提供了新思路。
Avian pathogenic Escherichia coli (APEC) is the causative agent of chicken colibacillosis. Paeoniflorin, a natural ingredient extracted from Paeonia lactiflora, has a variety of pharmacological effects including anti-inflammatory and immunomodulatory. However, its effects and mechanism in APEC-induced acute lung injury (ALI) in chicken is not clear. The aim of this study was to investigate the protective effect of paeoniflorin on APEC-induced ALI and its possible mechanism. Paeoniflorin (25, 50, and 100 mg/kg) was administered by gavage for 5 d starting at 9 d of age and the chicken were infected with APEC by intraperitoneal injection at 12 d of age. The tissues were collected after APEC infection for 36 h for analysis. The results showed that paeoniflorin significantly alleviated the symptoms, increased the survival rate and body weight gain of APEC-infected chicken, and improved the histopathological damages, and reduced APEC loads in lung tissues. In addition, paeoniflorin restored the gene expression of ZO-1, Occludin and Claudin-3 during APEC infection. Moreover, paeoniflorin pretreatment significantly affected the endocannabinoid system (ECs) by increasing DAGL, decreasing MAGL, increasing secretion of 2-AG. Then, paeoniflorin significantly decreased the secretion of IL-1β, IL-6 and TNF-α in lung tissues, and decreased the mRNA expression of CXCL8, CXCL12, CCL1, CCL5, and CCL17. In addition, paeoniflorin significantly reduced the phosphorylation levels of PI3K, AKT, P65, and IκB. In summary, we found that paeoniflorin inhibited APEC-induced ALI, and its mechanism may be through affecting ECs and inhibiting the activation of PI3K/AKT and NF-κB signaling pathways, which provides a new idea for the prevention and treatment of chicken colibacillosis.