Indole-3-propionic Acid Attenuates HI-Related Blood–Brain Barrier Injury in Neonatal Rats by Modulating the PXR Signaling Pathway

作者：Qianlei Zhao, Tingting Chen, Chao Ni, Yingying Hu, Yan Nan, Wei Lin, Yanli Liu, Feixia Zheng, Xulai Shi, Zhongdong Lin, Zhongdong Lin, Jianghu Zhu, Zhenlang Lin, Zhenlang Lin · 发表于：ACS Chemical Neuroscience · 年份：2022 · DOI：10.1021/acschemneuro.2c00418 · 被引用次数：37 · 研究领域：Barrier Structure and Function Studies、Neonatal and fetal brain pathology、Immune Response and Inflammation

The blood-brain barrier (BBB) is an important physiological barrier of the human body contributing to maintaining brain homeostasis and normal function. Hypoxic-ischemic (HI)-related brain injury is one of the main causes of neonatal acute morbidity and chronic disability. The previous research of our group confirmed that there was serious BBB destruction during HI brain injury. However, at present, the protection strategy of BBB is very limited, and further research on the protection mechanism is warranted. Indole-3-propionic acid (IPA) is a bacterial metabolism with anti-inflammatory and antioxidant properties, having neuroprotective effects and protective effects on the mucosal barrier. However, the role of IPA in BBB is not clear. In this research, we demonstrated the protective effect of IPA on BBB disruption from HI brain injury and hypothesized that it involves the amelioration of inflammation, oxidative stress, and MMP activation, thereby inhibiting apoptosis of rat brain microvascular endothelial cells (rBMECs). We demonstrated that expression levels of several inflammatory markers, including iNOS, TNF-α, IL-6, and IL-1β, were significantly increased from HI damage or OGD injury. However, IPA treatment inhibited the increase significantly. Moreover, we demonstrated that IPA reduced intracellular ROS levels and MMP activation in rBMECs from OGD injury. Further research on the underlying detailed molecular mechanisms suggested that IPA attenuates inflammation by inhibi...