胆酸对LPS诱导小鼠乳腺炎的保护作用及其机制

Protective effect and mechanism of cholic acid on LPS-induced mastitis in mice

乳腺炎是危害奶牛养殖业最为主要的疾病之一,严重制约着奶业的健康发展。抗生素作为乳腺炎的主要治疗药物,易造成细菌耐药性等问题。因此,寻找安全有效的方法或制剂替代抗生素对于乳腺炎的防治具有重要意义。胆酸(cholic acid, CA)作为机体的天然代谢产物,报道具有抑菌抗炎功能。本研究旨在探讨CA对脂多糖(LPS)诱导小鼠乳腺炎的保护作用及机制。将40只分娩后的BALB/c母鼠随机分为5组,包括空白对照组、LPS造模组、LPS+CA(10 mg/kg)组、LPS+CA(20 mg/kg)组和LPS+CA(30 mg/kg)组。通过对小鼠乳腺组织进行病理学观察、炎性细胞因子及相关信号通路检测等方法探究CA对LPS诱导小鼠乳腺炎的保护作用及机制。结果显示,CA呈剂量依赖性地改善LPS诱导小鼠乳腺组织病理损伤,显著降低髓过氧化物酶(MPO)活性和炎性细胞因子TNF-α和IL-1β的表达。进一步研究表明,CA显著抑制了LPS诱导的NF-κB信号通路激活,增加了法尼醇X受体(FXR)的表达。结果表明,CA通过上调FXR受体表达,进而抑制LPS诱导的NF-κB信号通路及炎性细胞因子产生,发挥对乳腺炎的保护作用。

Mastitis is one of the most important diseases endangering dairy farming, which seriously restricts the healthy development of dairy industry.As the main therapeutic drug for mastitis, antibiotics are likely to cause problems such as bacterial resistance.Therefore, finding safe and effective methods or preparations to replace antibiotics is of great significance for the prevention and treatment of mastitis.As a natural metabolite of the body, cholic acid(CA) has been reported to have antibacterial and anti-inflammatory functions.This study aimed to explore the protective effect of CA on LPS-induced mastitis in mice and related mechanisms.Forty BALB/c female mice after delivery were randomly divided into five groups: blank control group, LPS model, LPS+CA(10 mg/kg) group, LPS+CA(20 mg/kg) group, LPS+CA(30 mg/kg) group.The protective effect and mechanism of CA on LPS-induced mastitis in mice were explored through pathological observation of mouse breast tissue, detection of inflammatory cytokines and related signal pathways.The results showed that CA could improve the pathological damage of breast tissue in a dose-dependent manner, and significantly reduce the activity of myeloperoxidase(MPO) and the expression of inflammatory cytokines TNF-α and IL-1β.Further research showed that CA significantly inhibited the activation of the NF-κB signaling pathway induced by LPS and increased the expression of farnesoid X receptor(FXR).The above results indicate that CA inhibits the LPS-induced NF-κB signaling pathway and the production of inflammatory cytokines by up-regulating the expression of FXR receptors,and exerts a protective effect on mastitis.