Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

Abstract

The aim of the present study was to investigate the antioxidant mechanisms of dexmedetomidine against lung injury during intestinal ischemia reperfusion (iir) in rats. The model of iir-induced acute lung injury was established by occluding the superior mesenteric artery (SMa) for 1 h and reperfusing for 2 h using Sprague-dawley rats. Pathological examination was used to assess the extent of the lung injury. oxidative stress was evaluated by measuring malondialdehyde, myeloperoxidase and superoxide dismutase in the lung and plasma. The proinflammatory cytokines tumor necrosis factor-α and interleukin-6 were determined via an enzyme-linked immunosorbent assay. The mrna and protein expression of nuclear factor-erythroid 2 related factor 2 (nrf2) and heme oxygenase 1 (Ho-1) were determined using a reverse transcription-quantitative polymerase chain reaction and western blotting. Pretreatment with dexmedetomidine significantly inhibited the oxidative stress response and proinflammatory factor release caused by IIR compared with the normal saline group (Mda and Sod in lung and plasma, P<0.05; MPo, il-1β and TnF-α in lung and plasma, P<0.05). dexmedetomidine improved pulmonary pathological changes in iir rats compared with the normal saline group. investigations into the molecular mechanism revealed that dexmedetomidine increased the expression levels of nrf2 and Ho-1 via activating α2 adrenergic receptors compared with the normal saline group. The antagonism of α2 adrenergic receptors may reverse the protective effect of dexmedetomidine on lung injury during iir, including decreasing the expression levels of nrf2 and Ho-1, elevating the oxidative stress response and increasing the proinflammatory factor release. in conclusion, pretreatment with dexmedetomidine demonstrated protective effects against lung injury during iir via α2 adrenergic receptors. The nrf2/Ho-1 signaling pathway may serve a function in the protective effect of dexmedetomidine.

Dexmedetomidine Alleviates Lung Oxidative Stress Injury Induced by Ischemia-Reperfusion in Diabetic Rats via the Nrf2-Sulfiredoxin1 Pathway

“…We know that activation of Nrf2 protects against oxidative stress injury induced by ischemia-reperfusion injury. Previous studies [ 14 , 16 , 34 ] found that DEX restores the decline of Nrf2 activity induced by I/R injury or inflammation to the level of the control group. In their studies, the Nrf2 expression decreased in the “injury” group and DEX restores the decline of Nrf2 activity to the level of the control group, which was not exactly the same as our current research.…”

“…A previous study showed that nuclear factor erythroid 2-related factor (Nrf2) and its downstream protein sulfiredoxin1 participated in oxidative stress injury [ 13 ]. DEX pretreatment could activate the Nrf2 pathway in many organs in I/R models, such as the liver, brain, and intestines [ 14 – 16 ]. However, whether the effects of DEX on diabetic lung I/R injury are related to Nrf2-sulfiredoxin1-induced antioxidative effects is still unknown.…”

Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia–reperfusion-induced acute lung injury by activating AMPK signaling

“…Interestingly, STING inhibition through a selective inhibitor ( C-176 ) significantly attenuated pulmonary inflammation and fibrosis in mice induced by graphitized multiwalled carbon nanotubes [ 35 ]. As previously described, ALI is suggested to be induced by intestinal ischemia–reperfusion injury within 3 h after reperfusion [ 36 , 37 ]. Mitochondrial injury-induced activation of inflammatory factors and calcium overload can reportedly contribute to cleavages of the caspase family, including caspase-1 and caspase-3, at the early stage of reperfusion, which are indicators of pyroptosis and apoptosis [ 38 , 39 ].…”

Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway

“…Consistently, oxidative stress and inflammation have been attributed to the pathogenesis of intestinal I/R injury, while its reduction has been associated with the improvement in intestinal I/R injury [ 52 ]. Similarly, Chen et al verified that oxidative stress and inflammatory response are inhibited by Dex in rats with lung injury during intestinal I/R injury [ 53 ].…”