miR-146a-5p/TXNIP axis attenuates intestinal ischemia-reperfusion injury by inhibiting autophagy via the PRKAA/mTOR signaling pathway.

Autophagy is being increasingly recognized as an important regulator of intestinal ischemia-reperfusion(I/R)injury, but its exact role is still debated. Emerging evidence suggests that miR-146a-5p is involved in the initiation and development of I/R injury, but its role in intestinal I/R injury remains unclear. The present study generated an intestinal I/R mouse model and an oxygen glucose deprivation/reoxygenation (OGD/R) Caco-2 cell model and found that autophagy was increased and contributed to the intestinal injury and cell death induced by I/R and OGD/R. In addition, in both I/R and OGD/R models, the miR-146a-5p expression level was decreased and accompanied by an increase in TXNIP expression. By transfecting cells with an miR-146a-5p inhibitor or mimic, we observed that miR-146a-5p inhibits autophagy during OGD/R by targeting TXNIP; this was confirmed by the dual luciferase reporter gene assay. Additionally, through overexpression and knockdown cell lines, we established that TXNIP regulates autophagy during intestinal I/R via the PRKAA/mTOR pathway. The interaction between TXNIP and p-PRKAA was verified by immunofluorescence co-localization and immunoprecipitation assays. Moreover, we confirmed that TXNIP is indispensable for miR-146a-5p-mediated cell protection. Finally, we observed that miR-146a-5p overexpression inhibits autophagy and attenuates intestinal I/R injury via the PRKAA/mTOR pathway by targeting TXNIP in vivo. In conclusion, this study highlights the role of miR-146a-5p in regulating autophagy by targeting TXNIP, suggesting that miR-146a-5p may be a novel drug target for intestinal I/R therapy.

Effects of dexmedetomidine on lung ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To evaluate the effects of dexmedetomidine on lung ischemia-reperfusion (I/R) injury in rats.Methods Ninety-six healthy SPF male Wistar rats,weighing 250-350 g,aged 8-12 weeks,were randomly divided into 4 groups (n =24 each):sham operation group (S group),I/R group,low dose dexmedetomidine group (DL group) and high dose dexmedetomidine group (DH group).In DL and DH groups,dexmedetomidine 100 and 500 μg· kg-1 · d-1 were injected intraperitoneally once a day for 2 consecutive days,while the equal volume of normal saline was given in S and I/R groups.Lung·I/R was induced by clamping the left hilum of lung for 45 min followed by reperfusion at 30 min after administration on 2nd day.At 45 min of ischemia,and 60 and 120 min of reperfusion,6 rats were sacrificed,and lungswere removed for determination of TNF-α (tumor necrosis factor-a) content and myeloperoxidase (MPO) activity in lung tissues.The percentage of damaged alveolar in lung tissues was detected at 120 min of reperfusion.Another 6 rats were lavaged and the broncho-alveolar lavage fluid (BALF) was colleted for determination of the total protein concentrations.Results Compared with S group,the TNF-α content,MPO activity,percentage of damaged alveolar,and total protein concentrations in BALF were significantly increased in I/R,DL and DH groups.Compared with I/R group,the TNF-α content,MPO activity,percentage of damaged alveolar,and total protein concentrations in BALF were significantly decreased in DL and DH groups.Conclusion Dexmedetomidine can alleviate the lung I/R injury in rats,and the mechanism is related to inhibiton of the inflammatory responses.