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羟基红花黄色素 A 通过 TLR2 介导的 NF-κB 和 MAPK 通路抑制金黄色葡萄球菌诱导的小鼠子宫内膜炎。

Hydroxysafflor Yellow A Inhibits Staphylococcus aureus-Induced Mouse Endometrial Inflammation via TLR2-Mediated NF-kB and MAPK Pathway.

机构信息

Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Qingdao University, 20, Yuhuangding East Road, Yantai City, 264000, Shandong Province, China.

出版信息

Inflammation. 2021 Jun;44(3):835-845. doi: 10.1007/s10753-020-01297-8.

Abstract

The present study is designed to investigate the effect of hydroxysafflor yellow A (HYA) on Staphylococcus aureus (S. aureus)-induced mouse endometrial inflammation and to explore its molecular mechanism. We established a mouse endometritis model by intrauterine injection of S. aureus and intrauterine injection of HYA for treatment. Immunohistochemistry, immunofluorescence, and Western blot were used to detect protein expression in uterine tissue, and qPCR was used to measure mRNA expression. HYA could significantly weak uterine pathological changes caused by S. aureus and reduce MPO activity, CD45, CD3, and ED-1 protein expression in uterine tissues of S. aureus-infected mice. Similarly, HYA also significantly decreased S. aureus induced the increase in TNF-α, IL-1β, and IL-6 in uterine tissue. In vivo, we found that knockdown of TLR2 was very important could significantly reduce S. aureus induced the elevated expression of TNF-α, IL-1β, and IL-6 in mEECs. Importantly, in terine tissues of S. aureus-infected mice, HYA significantly decreased the ratio of p-p65/p65, p-IKBα/IKBα, p-p38/p38, p-Erk/Erk, and p-JNK/JNK expression. HYA displays anti-inflammatory effects on S. aureus mouse endometrial inflammation, and this effect might be related to HYA which could block TLR2-mediated NF-kB and MAPK pathway.

摘要

本研究旨在探讨羟基红花黄色素 A(HYA)对金黄色葡萄球菌(S. aureus)诱导的小鼠子宫内膜炎的影响,并探讨其分子机制。我们通过宫内注射 S. aureus 建立了小鼠子宫内膜炎模型,并通过宫内注射 HYA 进行治疗。采用免疫组织化学、免疫荧光和 Western blot 检测子宫组织中蛋白表达,采用 qPCR 检测 mRNA 表达。HYA 可显著减轻 S. aureus 引起的子宫组织病理学变化,降低感染小鼠子宫组织中 MPO 活性、CD45、CD3 和 ED-1 蛋白的表达。同样,HYA 也显著降低了 S. aureus 诱导的小鼠子宫组织中 TNF-α、IL-1β 和 IL-6 的增加。在体内,我们发现 TLR2 的敲低非常重要,可以显著降低 S. aureus 诱导的 TNF-α、IL-1β 和 IL-6 在 mEECs 中的表达升高。重要的是,在 S. aureus 感染小鼠的子宫组织中,HYA 显著降低了 p-p65/p65、p-IKBα/IKBα、p-p38/p38、p-Erk/Erk 和 p-JNK/JNK 表达的比值。HYA 对 S. aureus 诱导的小鼠子宫内膜炎具有抗炎作用,这种作用可能与 HYA 阻断 TLR2 介导的 NF-kB 和 MAPK 通路有关。

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