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| Effects of dexmedetomidine on cell apoptosis in lung tissue in a rat model of ventilator-induced lung injury
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| Qu Min, Mao Shun-hong, Jiao Bao-jie, Liu Xiang-ge, Yang Qiang, Shi Dan-dan, Ma Zhi-hong, Li Hui-zhi
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| The Second Department of Anesthesiology, Cangzhou Center Hospital, Cangzhou 061001, China
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Abstract Objective To investigate the effect of dexmedetomidine (DEX)on the apoptosis of lung tissue in a rat model of ventilator-induced lung injury. Methods One hundred pathogen-free male Sprague-Dawley rats, were randomly (random number) divided into 5 groups (n=20 each): the control group (group C), mechanical ventilation group (group V) and different dexmedetomidine doses of groups (DEX 1~3 group). Mechanical ventilation parameters: moisture content of 40 mL/kg, respiratory rate 50 breaths/min, I∶E ratio 1∶1, FiO2 is 21%. In DEX 1~3 groups: dexmedetomidine 0.5, 2.5, and 5.0 μg/kg were infused intravenously,respectively,over 20 min before ventilation,and then dexmedetomidine were infused intravenously for 4 h at a rate of 0.5, 2.5, and 5.0 μg/(kg·h), respectively,during mechanical ventilation. Immediately before tracheal intubation and at 1, 2 and 4 h of ventilation,blood samples were collected from the femoral artery for blood gas analysis, the PaO2 was recorded, and oxygen index was calculated. At 4 h of mechanical ventilation, the rats were sacrificed. Bronchial alveolar lavage fluid (BALF) was recycled to determine the lung permeability index (LPI), and the left lobe of the lungs was removed to determine the ratio of pulmonary wet/dry weight (W/D), and to detect of the expression of JNK, p-JNK, Bax, Bcl-2, Caspase-3 and BH3-only domain pro-apoptotic factor (BID, BIM) by Western blot. The expression of JNK mRNA was detected by RT-PCR. 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, group V and group DEX 1 OI decreased, W/D ratio, LPI, IAR, AI and the expression of BID, BIM increased, p-JNK and JNK mRNA were up-regulated, accompanied by increased expression of Bax, Caspase-3 , and decreased expression of Bcl-2 (P<0.05), and no significant change was found in the parameters mentiones above in group DEX 2,3 (P>0.05). Compared with the group V,the group DEX 2,3 OI were increased,ratio of W/D, LPI, IAR(%), AI(%) and the expression of BID, BIM decreased,p-JNK and JNK mRNA were down-regulated, accompanied by increased expression of Bax, Caspase-3, and increased expression of Bcl-2 (P<0.05), and no significant change was found in the parameters mentiones above in group DEX 2,3 (P>0.05). Compared with the group V, the pathological changes of lung tissues were significantly attenuated and cell apoptosis was reduced(by TUNEL assay)in DEX 2,3 groups. Conclusion The possible mechanism by which exmedetomidine mitigates ventilator-induced lung injury is inhibition of pulmonary tissue JNK signaling pathway activation, down-regulation of BH3-only domain pro-apoptotic factor (BID, BIM) expression, and then up-regulation of Bcl-2 expression,down-regulation of Bax expression,inhibition of Caspase-3 expression to reduce lung tissue apoptosis and reduce lung injury.
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Received: 28 July 2017
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Corresponding Authors:
Yang Qiang, E-mail:15103178181@139.com
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