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Abstract Title:

Tanshinone IIA improves sepsis-induced acute lung injury through the ROCK2/NF-κB axis.

Abstract Source:

Toxicol Appl Pharmacol. 2022 Apr 12 ;446:116021. Epub 2022 Apr 12. PMID: 35421429

Abstract Author(s):

Jie Liu, Yong-Hong Wu, Zheng-Liang Zhang, Ping Li

Article Affiliation:

Jie Liu

Abstract:

BACKGROUND: This research sought to explore the effects of Tanshinone IIA (TIIA) and its potential mechanism in sepsis-induced acute lung injury.

METHODS: 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).

RESULTS: 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.

CONCLUSION: 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.

Study Type : Animal Study

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