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| Effect of dexmedetomidine on endoplasmic reticulum stress in lung tissue of rats with ventilation-associated lung injury and its relationship with PI3K/Akt signaling pathway |
| Qu Min, Mao Shun-hong, Jiao Bao-jie, Liu Xiang-ge, Yang Qiang, Shi Dan-dan, Wang Ya-li, Ma Zhi-hong, Li Hui-zhi |
| The Second Department of Anesthesiology, Cangzhou Center Hospital, Cangzhou 061001, China |
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Abstract Objective To investigate the effects of dexmedetomidine on endoplasmic reticulum stress-induced apoptosis and PI3K/Akt signaling pathway in rats with ventilation-associated lung injury. Methods Eighty Sprague-Dawly (SD) rats were randomly (random number) divided into 4 groups (n=20 each): the control group (Group C), Mechanical ventilation Group (Group V), Dexmedetomidine groups (Group D) and Dexmedetomidine +LY294002 group (group DL). Group C, no mechanical ventilation, and breathed independently; Mechanical ventilation in group V, D and DL for 4 h, dexmedetomidine 5.0 μg/(kg·h) were infused intravenously, 20 min before mechanical ventilation, 5.0μg/(kg·h) intravenous infusion during mechanical ventilation. In the Group DL, LY294002 0.3 mg/kg was infused intravenously 5 min prior to dexmedetomidine. Group V was given normal saline. Rats were sacrificed at 4 hours after mechanical ventilation and the lung permeability index (LPI) and lung wet/dry weight (W/D) ratio were measured. Western blot was used to detect the level of Akt, phosphorylated Akt (P-Akt), glucose-regulated protein 78 (GRP78), CAAT enhancer binding protein homologous protein (CHOP), and caspase-12. The pathological changes of lung tissues were observed under light microscope, and the alveolar injury rate (IAR) was determined. The lung cell apoptosis was observed and apoptosis index was calculated by TUNEL method. Results Compared with the group C, ratio of W/D, LPI, IAR(%), AI(%) in group V and group DL increased, and the expressions of GRP78,CHOP, caspase-12 increased (group C: 0.35±0.02, 0.28±0.02, 0.51±0.03; group V: 1.27±0.11, 1.09±0.13, 1.37±0.15; group DL: 0.97±0.08, 0.66±0.07, 1.01±0.09; P<0.05), the expression of P-Akt decreased (group C: 0.81±0.04; group V: 0.23±0.01; group DL:0.44±0.02; P<0.05). Compared with the group V, group D and group DL Ratio of W/D, LPI, IAR(%), AI(%) decreased, and the expressions of GRP78,CHOP, caspase-12 decreased (group V: 1.27±0.11, 1.09±0.13, 1.37±0.15; group DL: 0.97±0.08, 0.66±0.07, 1.01±0.09; group D: 0.62±0.04, 0.43±0.05, 0.79±0.07; P<0.05), the expression of P-Akt increased (group V: 0.23± 0.01; group DL: 0.44±0.02; group D: 0.65±0.03; P<0.05), the pathological changes of lung tissues were significantly attenuated; Compared with the group D, ratio of W/D, LPI, IAR(%), AI (%) in group DL increased, and the expressions of GRP78, CHOP, caspase-12 increased (group D: 0.62±0.04, 0.43±0.05, 0.79±0.07; group DL: 0.97±0.08, 0.66±0.07, 1.01±0.09; P<0.05), the expression of P-Akt decreased (group D: 0.65±0.03; group DL: 0.44±0.02; P<0.05), and the lung tissue pathological damage was heavier. Conclusion Dextomidine can alleviate ventilation-associated lung injury in rats, which is related to activation of PI3K/Akt signaling pathway, inhibition of endoplasmic reticulum stress, and reduction of apoptosis in lung tissue.
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Corresponding Authors:
Yang Qiang, E-mail: 15103178181@139.com
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