Dexmedetomidine alleviates blunt chest trauma and hemorrhagic shock‑resuscitation‑induced acute lung injury through inhibiting the NLRP3 inflammasome

Abstract

Blunt chest trauma with hemorrhagic shock frequently induces pulmonary inflammation that leads to acute lung injury (ali). The present study aimed to explore the protective effects of dexmedetomidine (dex) in blunt chest trauma and hemorrhagic shock-resuscitation (THSr)-induced ali by mediating nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome formation in rats. An ALI model in rats induced by THSr was constructed and dex was administered intraperitoneally (5 µg/kg/h) immediately after blunt chest trauma. Blood samples were collected for the determination of proinflammatory factor levels, and lung tissue specimens were harvested for wet/dry (W/d) weight ratio, hematoxylin and eosin staining, and transmission electron microscopy analyses. additionally, malondialdehyde (Mda), superoxide dismutase (Sod), lactate dehydrogenase (ldH) and myeloperoxidase (MPo) activity were evaluated, and the expression of protein in lung tissues was examined via western blot analysis. compared with the sham group, pathological alterations in the ali group and the W/d ratios were significantly increased. Mda, ldH and MPo activity, and the levels of interleukin (il)-1β, il-18, il-6 and tumor necrosis factor-α were significantly elevated. NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain and caspase-1 expression was significantly increased. Conversely, Dex treatment significantly reversed these changes. The present study demonstrated that by reducing inflammatory responses, dex exerted protective effects against THSr-ali in rats, potentially via the inhibition of nlrP3 signaling pathways.

Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway

“…Similarly, we observed that YOH administration reversed the effect of Dex of the inflammatory response and cognitive impairment. Moreover, the administration of YOH with DEX increased the level of NLRP3 and ASC expression compared to the Dex only group, consistent with results obtained in previous studies [ 36 , 37 ]. Therefore, present study confirmed that the effects of Dex on the POCD condition are executed by directly regulating level of NLRP3 and ASC expression and activation.…”

Dexmedetomidine alleviates pulmonary edema through the epithelial sodium channel (ENaC) via the PI3K/Akt/Nedd4-2 pathway in LPS-induced acute lung injury

“…The data are presented as the means ± SD. **P < 0.01 vs the control group; ***P < 0.001 vs the control group [26][27][28]; our previous studies also confirmed that TNF-α and IL-1β concentrations in lung tissues are significantly increased in LPS-induced ALI models, while Dex reduces TNF-α and IL-1β concentrations [17]. Consistent with these studies, our study revealed that Dex reduced TNF-α, IL-1β, and IL-6 concentrations and increased IL-10 concentrations in BALF, suggesting that Dex may be beneficial for regulating the balance of inflammatory responses.…”

Hemorrhagic Shock Assessed by Tissue Microcirculatory Monitoring: A Narrative Review

“…Trauma seriously threatens the lives of young adults and accounts for a significant proportion of the global disease burden (1). Hemorrhagic shock (HS) is a common type of hypovolemic shock and posttraumatic complication and has a mortality rate of up to 40% (2,3). Hemorrhagic shock is also the leading cause of death and a potential preventable cause of death in trauma patients.…”