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黄芩苷通过 NF-κB 和 JNK 信号通路减轻大肠杆菌和金黄色葡萄球菌感染致兔子宫内膜炎。

Baicalin attenuates endometritis in a rabbit model induced by infection with Escherichia coli and Staphylococcus aureus via NF-κB and JNK signaling pathways.

机构信息

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin 150030, China.

College of Life Science, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin 150030, China.

出版信息

Domest Anim Endocrinol. 2021 Jan;74:106508. doi: 10.1016/j.domaniend.2020.106508. Epub 2020 Jun 9.

Abstract

In this study, a rabbit endometritis model was developed to study cow endometritis. In addition, the protective effects of baicalin (a flavonoid) against endometritis were investigated. Clinical symptoms, differential leukocyte counting, uterine secretion smear microscopy and chemical examination, urine testing, and signs of necropsy showed abnormal changes and inflammatory responses in the uterus of rabbits. Histopathological results revealed visible inflammatory exudates and blood spots between intercellular spaces which confirmed that the rabbit endometritis model was successfully developed. Most importantly, these inflammatory signs were partially attenuated with baicalin treatment. The data revealed that the increased body temperature and leukocyte cells, pus, and the detachment of epithelial cells were alleviated with baicalin administration in a dose-dependent manner. Histopathological tissue changes such as inflammatory cells infiltrates, hyperemia, hemorrhages, and shedding of epithelial cells were partially attenuated with baicalin treatment. In addition, the mRNA expression of inflammation-related genes (iNOS, IL-1β, TNF-α, IL-10, IL-4, and IL-6) was significantly altered in RAW264.7 cells after LPS treatment. Further, the phosphorylated protein expression of JNK, p65, and IκBα were significantly reduced with LPS treatment. Intriguingly, baicalin pretreatment reversed the alteration in mRNA expression of inflammation-related genes and significantly reduced the phosphorylation of JNK, p65, and IκBα. In summary, our results suggest that baicalin has protective effects on bacterial-induced endometritis in rabbits that involve the suppression of NF-κB and JNK signaling pathways and pro-inflammatory cytokines.

摘要

本研究构建了兔子宫内膜炎模型来研究奶牛子宫内膜炎,并探讨了黄芩素(一种黄酮类化合物)对子宫内膜炎的保护作用。临床症状、白细胞分类计数、子宫分泌物涂片显微镜检查和化学检查、尿液检查以及剖检迹象显示,兔子的子宫出现了异常变化和炎症反应。组织病理学结果显示,细胞间可见明显的炎性渗出物和血斑,证实成功建立了兔子宫内膜炎模型。重要的是,黄芩素治疗部分减轻了这些炎症迹象。数据显示,黄芩素治疗呈剂量依赖性地减轻了体温和白细胞细胞的升高、脓性分泌物和上皮细胞脱落。黄芩素治疗还部分减轻了组织学变化,如炎性细胞浸润、充血、出血和上皮细胞脱落。此外,LPS 处理后 RAW264.7 细胞中与炎症相关的基因(iNOS、IL-1β、TNF-α、IL-10、IL-4 和 IL-6)的 mRNA 表达显著改变。进一步研究发现,LPS 处理后 JNK、p65 和 IκBα 的磷酸化蛋白表达显著降低。有趣的是,黄芩素预处理逆转了与炎症相关的基因 mRNA 表达的改变,并显著降低了 JNK、p65 和 IκBα 的磷酸化。综上所述,本研究结果提示,黄芩素对兔细菌性子宫内膜炎具有保护作用,其机制可能与抑制 NF-κB 和 JNK 信号通路以及促炎细胞因子有关。

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