Abstract
Objective: The aim of the present study is to investigate the anti-injury and anti-inflammatory effects of dexmedetomidine (Dex) in acute liver injury induced by lipopolysaccharide (LPS) in Sprague–Dawley rats and its possible mechanism.Methods: The acute liver injury model of male rats was established by injecting LPS into tail vein. The mean arterial pressure (MAP) of rats was recorded at 0–7 h, and lactic acid was detected at different time points. Wet/dry weight ratio (W/D) was calculated. Pathological changes of rat liver were observed by HE staining. ALT and AST levels in serum were detected. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) in liver tissue homogenate and the levels of IL-1β and IL-18 in serum were detected by ELISA. Protein levels of Caveolin-1 (Cav-1), TLR-4 and NLRP3 in liver tissue were tested by immunohistochemistry method. The expression of Cav-1, TLR-4 and NLRP3 mRNA in liver tissue was detected by quantitative polymerase chain reaction (qPCR) to explore its related mechanism.Results: Compared with NS group, serum lactic acid, W/D of liver tissue, MPO, SOD, IL-1β and IL-18 were significantly increased and MAP decreased significantly in LPS group and D+L group. However, compared with NS group, D group showed no significant difference in various indicators. Compared with LPS group, MPO, SOD, IL-1β and IL-18 were significantly decreased and MAP was significantly increased in D+L group. D+L group could significantly increase the level of Cav-1 protein and decrease the level of TLR-4 and NLRP3 protein in liver tissue caused by sepsis. The expression of Cav-1 mRNA was significantly up-regulated and the expression of TLR-4 and NLRP3 mRNA was inhibited in D+L group.Conclusion: Dex pretreatment protects against LPS-induced actue liver injury via inhibiting the activation of the NLRP3 signaling pathway by up-regulating the expression of Cav-1 by sepsis.
Highlights
Acute liver failure (ALF) is an extremely serious clinical syndrome caused by various factors
Most studies have shown that its downstream molecule is Caveolin-1 (Cav-1) protein, which may be involved in the regulation of TLR-4-mediated inflammation [4] and plays an important role in the occurrence and development of acute liver injury
Acute liver injury model induced by LPS Before the beginning of the experiment, the rats were weighed and recorded, and the rats were placed on a constant temperature heating pad
Summary
Acute liver failure (ALF) is an extremely serious clinical syndrome caused by various factors. More and more studies have indicated that dexmetomidine may reduce the degree of acute liver injury caused by sepsis by inhibiting the release of pro-inflammatory cytokines mediated by TLR-4 signal pathway [2,3]. Studies have shown that dexmetomidine can participate in the regulation of TLR-4-mediated inflammation through Cav-1 protein [5,6], which plays an important role in the occurrence and development of acute liver injury. The effects of dexmedetomidine on inflammatory response, especially Cav-1, TLR-4 and NLRP3, were observed in rats with acute liver injury stimulated by lipopolysaccharide (LPS). This may be at least part of the mechanism that dexmetomidine inhibits TLR-4-mediated inflammatory signaling pathway. The present study will provide new insights into the mechanism of dexmedetomidine in reducing acute liver injury and provide a theoretical basis for clinical treatment of dexmetomidine
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