Effects of rapamycin pretreatment on lung injury caused by hepatic cold ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the effects of rapamycin pretreatment on lung injury caused by hepatic cold ischemia-reperfusion (I/R) injury in rats.Methods Twenty-four healthy male Sprague-Dawley rats,aged 8-10 weeks,weighing 220-250 g,were randomly divided into 3 groups (n =8 each):sham operation group (S group),lung injury caused by hepatic cold I/R injury group (I/R group),and rapamycin pretreatment group (RP group).Laparotomy was performed,and hepatic lobes and related blood vessels were only isolated in group S.Hepatic cold I/R was induced in I/R and RP groups.Rapamycin 10 mg· kg-1 ·d-1 was injected through a gastric tube into stomach for 3 consecutive days before surgery in RP group.The rats were sacrificed at 12 h of reperfusion,and lungs were removed to detect the levels of malondialdehyde (MDA),superoxide dismutase (SOD)and nitric oxide (NO),iNOS mRNA expression (by RT-PCR),tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression (by immuno-histochemistry) in lung tissues and for examination of the pathological changes of lungs with light microscope.Results Compared with S group,the levels of MDA,NO,iNOS mRNA,TNF-α and IL-6 were significantly increased and the SOD activity was decreased in I/R and RP groups (P ＜0.05).The SOD activity was significantly higher,and the levels of MDA,NO,iNOS mRNA,TNF-α and IL-6 wee lower in group RP than in I/R group (P ＜ 0.05).The pathological changes of lungs were significantly attenuated in RP group as compared with I/R group.Conclusion Rapamycin pretreatment can reduce lung injury caused by hepatic cold I/R injury in rats,and inhibition of iNOS expression,reduction of NO product and decrease in inflammatory responses are involved in the mechanism. Key words: Sirolimus; Liver; Respiratory distress syndrome, adult; Reperfusion injury