Influence of potassium channel opener postconditioning on rat's lung injury

Abstract

Objective To explore influnence of diazoxide,potassium channel opener,postconditioning on cell apoptosis during systemic-pulmonary ischemia reperfusion injury (LIRI) of rat model.Methods A total of 50 SD rats were divided into five groups at random:Sham operation group (Sham group),ischemia reperfusion group (I/R group),ischemic postconditioning group (IPO group),diazoxide postconditioning group (DE group) and combination postconditioning group of Diazoxide and 5-Hydroxy decanoic acid (5-HD) (DE + 5-HD group).Lung tissue cell apoptotic index (AI) was determined and the expression levels of cysteine aspartate specific protease-3 (Caspase-3),B cell lymphoma/leukemia-2 (bcl-2) and bcl-2 associated X protein (bax) in lung tissue were determined,in addition,morphopathology of lung tissue was observed using light and electron microscope.Results Compared with Sham group,AI values in I/R and DE + 5-HD groups were increased significantly [I/R group (32.42 ± 4.57) ％ vs.Sham group (1.87 ± 0.37) ％,DE + 5-HD group (31.51 ± 5.33) ％ vs.Sham group (1.87 ± 0.37) ％,(P ＜ 0.05)] ; expression levels of Caspase-3 was increased significantly [I/R group (0.83 ± 0.07) vs.Sham group (0.44 ±0.04),DE+5-HD group (0.81 ±0.07) vs.Sham group (0.44 ±0.04),P＜0.05] ; ratios between bcl-2 and bax were decreased significantly [I/R group (1.20 ± 0.16) vs.Sham group (1.45±0.10),DE+5-HD group (1.22±0.15) vs.Sham group (1.45 ±0.10),P＜0.05];compared with I/R and DE + 5-HD groups,AI values in IPO and DE groups were decreased significantly [IPO (15.43 ±2.32)％ or DE group (15.19 ±3.46)％ vs.I/R (32.42 ±4.57)％ or DE +5-HD group (31.51 ± 5.33) ％,P ＜ 0.05] ; expression levels of Caspase-3 were decreased significantly [IPO (0.69 ±0.05)or DE group (0.65 ±0.04) vs.I/R (0.83 ±0.07) or DE +5-HD group (0.81 ±0.07),P ＜ 0.05] ; ratios between bcl-2 and bax were increased significantly [IPO (1.84 ± 0.33) or DE group (1.86±0.27) vs.I/R (1.20±0.16) or DE+5-HDgroup (1.22±0.15),P＜0.05]; while that of bcl-2 in lung tissue was higher significantly in Levo group,compared with I/R and Levo + 5-HD group (P ＜ 0.05) ; no significant differences of individual indicators were found during comparisons between I/R and DE + 5-HD groups as well as IPO and DE groups.Conclusion LIRI can be alleviated by Diazoxide stimulating IPO protective function and possible lung protective mechanism may involve opening of mitoKATP,relieving of Ca2+ overload,up-regulating of expression level of bcl-2 and down-regulating that of Caspase-3 as well as bax. Key words: Lung injury; Ischemic postconditioning; Diazoxide