Artesunate Inhibits Renal Ischemia-Reperfusion-Mediated Remote Lung Inflammation Through Attenuating ROS-Induced Activat
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ORIGINAL ARTICLE
Artesunate Inhibits Renal Ischemia-Reperfusion-Mediated Remote Lung Inflammation Through Attenuating ROS-Induced Activation of NLRP3 Inflammasome Zhaohui Liu ,1,2 Min Qu,1 Lili Yu,1 Panpan Song,1 and Yulin Chang1
The molecular mechanisms of acute lung injury (ALI) are closely associated with nucleotide-binding domains and leucine-rich repeat (NLR) pyrin domains containing 3 (NLRP3) inflammasome, in which alveolar macrophages (AMs) exert an essential function. Our study has been proved that artesunate (AS) inhibits ALI. Nevertheless, the inhibition actions of AS on activation of NLRP3 in renal ischemia-reperfusion (RIR)-mediated ALI remain to be further discussed. Male Sprague-Dawley rats were randomly assigned into four groups: sham + NS, sham + AS, RIR + NS, and RIR + AS. RIR-mediated ALI was performed through bilateral renal pedicle occlusion for 60 min followed by reperfusion for 24 h. AS (15 mg/kg) or NS was injected intraperitoneal to rat 1 h before RIR treatment. AMs were rendered hypoxic (0.5%) for 2 h and reoxygenated for 24 h. Lung injury index and histology, and inflammatory cells and cytokine release in the BALF and AMs were examined. The protein and mRNA levels of NLRP3, ASC, and caspase-1 in the lung and AMs were evaluated via Western blot and real-time RCR. In this research, we indicated that AS preconditioning inhibited RIR-mediated lung damage, vascular permeability, and edema in rats. AS reduced RIR-mediated ALI, as characterized by abatement in the count of inflammatory cells, and the production of inflammatory cytokines in the BALF. AS administration inhibited the number of F4/80-positive cells, the activity of myeloperoxidase, and the fiery cytokines mRNA expression in lung samples of RIR-stimulated rats. Furthermore, AS alleviated the activity of caspase-1 and activation of NLRP3 through depending on reactive oxygen species (ROS). An in vitro finding that AS mitigated hypoxia/reoxygenationmediated activation of AMs partially supported in vivo study. In a word, these findings demonstrate that AS pretreatment attenuated RIR-mediated ALI potentially through reducing ROS-induced activation of the NLRP3 inflammasome. Abstract—
KEY WORDS: acute lung injury; renal ischemia-reperfusion injury; artesunate; nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3; reactive oxygen species.
INTRODUCTION 1
Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, No.16 Xinhua West Road, Yunhe District, Cangzhou, Hebei, China 2 To whom correspondence should be addressed at Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, No.16 Xinhua West Road, Yunhe District, Cangzhou, Hebei, China. E-mail: [email protected]
Acute lung injury (ALI) is a familiar and lethal medical disease [1]. ALI is evidenced by extensive inflammatory responses [2]. These signs bring about lung edema, lung hemorrhage, and severely afflicted lung ventilation disorder [3]. In the recent several tens of years, although
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