Effect of dexmedetomidine pretreatment on ERK pathway during acute lung injury in a rat model of liver transplantation / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effects of dexmedetomidine pretreatment on extracellular sig?nal?regulated kinase ( ERK) pathway during acute lung injury in a rat model of liver transplantation. Meth?ods Sixty male Sprague?Dawley rats, weighing 235-250 g, were divided into 4 groups ( n=15 each) u?sing a random number table sham operation group (group S), liver transplantation group (group LT), low?dose dexmedetomidine pretreatment group ( group LD ) and high?dose dexmedetomidine pretreatment group ( group HD) . In LT, LD and HD groups, the model of orthotopic liver transplantation was estab?lished, and the operation time was about 4 h. Dexmedetomidine 2?5 and 5?0μg·kg-1 ·h-1 were intrave?nously infused for 1 h starting from 1 h prior to clipping the hepatic artery and portal vein in LD and HD groups, respectively. The rats were sacrificed after the end of operation, and the lungs were removed for determination of wet to dry weight ratio ( W∕D ratio) , cell apoptosis and expression of ERK mRNA, ERK, phosphorylated ERK ( p?ERK) , Bcl?2 and Bax in lung tissues and for examination of the pathological chan?ges ( with light microscope) and ultrastructure of lung tissues ( with transmission electron microscope) . The injured alveolus rate ( IAR) , apoptosis index ( AI) and ratio of Bcl?2 to Bax expression ( Bcl?2∕Bax ratio) were calculated. Results Compared to group S, the W∕D ratio, IAR, AI, expression of ERK?1 mRNA, ERK?2 mRNA, p?ERK, Bcl?2 and Bax and Bcl?2∕Bax ratio were significantly increased in LT, LD and HD groups ( P<0?05) . Compared to group LT, the W∕D ratio, IAR and AI were significantly decreased, the expression of ERK?1 mRNA, ERK?2 mRNA, p?ERK and Bcl?2 and Bcl?2∕Bax ratio were significantly increased, and the expression of Bax was significantly down?regulated in LD and HD groups (P<0?05). Compared to group LD, the W∕D ratio, IAR and AI were significantly decreased, the expression of ERK?1 mRNA, ERK?2 mRNA, p?ERK and Bcl?2 and Bcl?2∕Bax ratio were significantly increased, and the ex?pression of Bax was significantly down?regulated in group HD ( P<0?05) . The pathological changes of lung tissues were significantly attenuated in LD and HD groups as compared with group LT, and in group HD as compared with group LD. Conclusion The mechanism by which dexmedetomidine pretreatment mitigates cell apoptosis during acute lung injury is related to activation of ERK pathway in a rat model of liver trans?plantation.