The Effect of Dexmedetomidine Post-treatment on the Inflammatory Response of Astrocyte Induced by Lipopolysaccharide

Abstract

To explore the effect of dexmedetomidine (DEX) post-treatment on the inflammatory response of astrocyte induced by lipopolysaccharide (LPS). The astrocytes of neonatal mice were primarily cultured in vitro. After purification and identification, the cells were divided into five groups: group C: control group; group L: astrocytes were treated with 1 μg/ml LPS for 24 h; group D1, D2, and D3: astrocytes were pretreated with 1 μg/ml for 24 h LPS, and then cultured with low (0.1 μM), medium (1 μM), high (10 μM) concentration of DEX for 30 min, respectively. The cell survival rate was detected by cell counting kit. The expressions of inducible nitric oxide synthase (iNOS) mRNA, tumor necrosis gactor-α (TNF-α) mRNA, and interleukin-1β (IL-1β) mRNA were measured by RT-PCR in cell lysis solution of every group. The concentration of nitric oxide (NO) was detected by Griess method. The concentrations of IL-1β and TNF-α were measured, respectively, by enzyme-linked immuno sorbent assay. Compared with the group C, the expressions of iNOS mRNA, TNF-α mRNA, and IL-1βm RNA were significantly up-regulated, the release of NO, TNF-α, and IL-1β was significantly increased in group L (P < 0.05). Compared with group L, mRNA levels of inflammation-related factors and release of inflammatory factors were significantly down-regulated in group D2 and D3 (P < 0.05). There was no statistical difference between group D1 and group L. Pre-treatment with medium and high concentration of DEX can inhibit the LPS-induced inflammatory response of astrocyte.

Organ-Protective Effects and the Underlying Mechanism of Dexmedetomidine

“…In sepsis rats, Taniguchi et al [102] found that the medium dose (5 μg/kg/h) and high dose (10 μg/k/h) of DEX reduce plasma levels of TNF-α and IL-6, while the low-dose group (2.5 μg/kg/h) showed no decreasing effect. Similar experimental phenomena were observed in vitro [43,103]. Lai et al [104] believed that the anti-inflammatory effect of DEX had a parabolic relationship with its concentration.…”

Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine

“…In our previous study, dexmedetomidine reduced mechanical allodynia and hyperalgesia in a chronic constriction injury model of neuropathic pain [Farghaly et al, 2014]. Another study revealed that dexmedetomidine reduced hippocampal levels of cytokines in various pain conditions [Tanabe et al, 2014;Xie et al, 2015;Farghaly et al, 2016;Zhu et al, 2016]. They suggested that stimulation of α 2 -receptors during stress causes modulation of cytokine production by monocytes and macrophages, independently of adenylyl cyclase cAMP.…”

“…In addition to its sedative and analgesic effects, many studies proved its anti-inflammatory effect. It attenuates lipopolysaccharide-induced cytokine expression in astrocytes [Xie et al, 2015]. Through α 2A -adrenergic receptors, it suppresses mRNA of MCP-1, a proinflammatory cytokine [Liu et al, 2017].…”

The effect of dexmedetomidine premedication on postoperative systemic inflammatory response in children undergoing hernia repair surgery: A randomized controlled trial

“…The effects of dexmedetomidine on inflammation have been demonstrated in some clinical settings and studies. Medium and high concentrations of dexmedetomidine inhibited the expression and release of inflammatory factors in mice 11 . Adult patients receiving a 1.0 μg/kg loading dose of dexmedetomidine followed by infusion at 0.5 μg/kg/h for laparoscopic cholecystectomy showed a decreased inflammatory response 12 .…”