Dexmedetomidine may upregulate the expression of caveolin-1 in lung tissues of rats with sepsis and improve the short-term outcome

Abstract

Dexmedetomidine (DXM) is a selective α2-adrenoceptor (α2-AR) and imidazoline receptor (IR) agonist that has been reported to regulate inflammatory responses mediated by diverse signaling pathways through α2-AR. The majority of the reported receptors or downstream molecules have been demonstrated to locate with caveolin-1, a protein suggested to participate in regulating Toll-like receptor 4 (TLR4)-mediated inflammatory responses and the pathogen endocytosis capability of macrophages. The present study hypothesized that DXM may influence these pathways by regulating the expression of caveolin-1 and mediating the subsequent effects. Using a cecal-ligation and puncture-induced rat sepsis model, it was initially observed that pre-emptive DXM is able to upregulate and stabilize the amount of caveolin-1 expression, which may be partly antagonized by both α2-AR and the IR antagonist atepamezole (APZ). The pathophysiological parameters indicated that DXM is able to inhibit secondary lung injury, in addition to the rise of body temperature and arterial lactate accumulation, however it marginally increased arterial glucose and the murine sepsis score, which can be largely antagonized by APZ. The overall effect was beneficial and improved the 24-h cumulative survival rate of rats with sepsis. In conclusion, preemptive clinical sedative doses of DXM may upregulate the expression of caveolin-1 downregulated by sepsis, which may contribute to the inhibition of inflammatory pathways such as TLR4-mediated pathways. Furthermore, DXM may favor the improvement of short-term outcomes by the regulation of other metabolic pathways.

The effect of dexmedetomidine and clonidine on the inflammatory response in critical illness: a systematic review of animal and human studies

“…The nine CLP models were undertaken in rats [17, 21–23, 34, 41, 42] and mice [36, 37]. Seven studies used dexmedetomidine [17, 22, 23, 34, 36, 37, 41, 42] and one clonidine [21]. Study size ranged from 21 to 210 animals with a range of control group designs.…”

“…Routes of administration were intraperitoneal [22, 36, 41, 42] and intravenous [17, 21, 23, 34, 37] as well as bolus [21–23, 36, 37, 41, 42] versus infusion [17, 34]. Study design included pre-only groups [34, 42], pre/post groups [21, 36], and post-only [17, 22, 23, 37, 41] designs. Three studies included α2 agonist blockade groups [17, 23, 42].…”

Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo

“…Because the overproduction of inflammation has been implicated in the development and maintenance of ALI, early potent interventions to control liver injury development are particularly important. The pharmacological effects of DEX mainly concentrated on anti-inflammatory ( Tolaj et al, 2017 ), immunosuppressive ( Wang et al, 2013 ), anti-endotoxic ( Zhang et al, 2017 ), and anti-shock ( Yang et al, 2010 ) effects. While researchers have demonstrated that DEX has shown the ability to enhance the resistance of organ injury and improve the outcome of infection, its limitation is that it cannot be used for a long time ( Kengatharan et al, 1996 ; Wang et al, 2013 ; Sun et al, 2017 ).…”

Ginsenoside Rg3 attenuates sepsis-induced injury and mitochondrial dysfunction in liver via AMPK-mediated autophagy flux

“…Although much progress has been made in the early treatment of those with septic shock, people know little about the pathogenesis of organ dysfunction triggered by septicemia. Sepsis features the activation of systemic inflammatory pathway within blood vessels, by which potent inflammatory mediators are released into the blood, thus leading to septic shock, multiple organ dysfunction, adverse clinical outcomes, and high mortality [ 1 , 2 ]. As an important visceral organ, liver has multiple metabolic functions, such as composition, decomposition, detoxication, and immunity, and during sepsis-induced MODS, it is one of the important organs most frequently implicated by sepsis [ 3 , 4 ].…”