细胞凋亡
岩石2
炎症
体内
生物
肺
流式细胞术
促炎细胞因子
癌症研究
细胞生物学
免疫学
医学
信号转导
罗亚
内科学
生物化学
生物技术
作者
Jie Liu,Yonghong Wu,Zhengliang Zhang,Ping Li
标识
DOI:10.1016/j.taap.2022.116021
摘要
This research sought to explore the effects of Tanshinone IIA (TIIA) and its potential mechanism in sepsis-induced acute lung injury. Cecal ligation and puncture (CLP) was performed to construct a sepsis model in vivo. RLE-6TN cells were treated with lipopolysaccharide (LPS) to establish a sepsis model for in vitro experiments. The histopathological changes of the lung tissues were scored using HE staining, IHC, and dry and wet method. Apoptosis in the lung tissues was detected by TUNEL assay. Meanwhile, ELISA was used to determine the levels of the pro-inflammatory factors. Cell proliferation and apoptosis were evaluated using CCK-8, EdU assays and flow cytometry, respectively. RT-qPCR analysis was carried out to measure the expression of Rho associated coiled-coil containing protein kinase 2 (ROCK2). TIIA dramatically alleviated the pathological injuries of the lung, and relieved apoptosis, neutrophil infiltration, lung edema and inflammation response. Highly expressed ROCK2 was observed in septic rats in vivo and LPS-induced RLE-6TN cells in vitro. We found that ROCK2 knockdown promoted cell proliferation, and inhibited cell apoptosis and inflammation in LPS-treated RLE-6TN cells. Moreover, TIIA improved LPS-caused injury in RLE-6TN cells through downregulating ROCK2 expression. Mechanistically, TIIA repressed LPS-caused activation of the NF-κB pathway by regulating ROCK2 in RLE-6TN cells. Additionally, TIIA assuaged CLP-induced lung injury in the rats via downregulating ROCK2 to inactivate the NF-κB pathway in vivo. Our data demonstrated that TIIA improved sepsis-induced lung injury by downregulating ROCK2 and further inactivating the NF-κB signaling pathway in vivo and in vitro.
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