摘要
目的观察K+-ATP通道活化剂二氮嗪(Diazoxide)对实验性(Sprague-Dawley,SD)大鼠在体状态下缺血再灌注损伤的保护作用并探讨其发生的机制。方法60只健康雄性SD大鼠随机分为5组,分别为假手术对照组(Control组,n=12),缺血再灌注组(ischemia-reperfusion,I/R组,n=12),二氮嗪药物防治组(Diazoxide组,n=12),二氮嗪的抑制剂组(K+-ATP通道阻断剂):包括二氮嗪+格列苯脲(Diazoxide+Glibenclamide组)组(n=12)和二氮嗪+5-羟基酸组(5-hydroxydecanoate,5-HD,Diazoxide+5-HD组,n=12)。缺血时间为1h,再灌注时间为30min。比较5组肺脏的干湿比(Wet/Dry Ratio,W/D),并对5组再灌注后肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中的乳酸脱氢酶(lactate dehydrogenase,LDH)和再灌注前后肺泡液体清除率(alveolar fluid clearance,AFC)进行了测定。结果Diazoxide组的W/D虽然仍高于Control组,但是和I/R组相比明显降低,差异有显著性(P<0.01)。Diazoxide组的LDH比I/R组明显降低,并且Diazoxide组的再灌注前后的AFC明显高于I/R组和二氮嗪的抑制剂组。Diazoxide组的LDH和AFC与I/R组以及应用抑制剂组相比差异有显著性(P<0.01)。结论二氮嗪可以提高AFC,减轻再灌注组的肺水肿和肺损伤的程度。二氮嗪的抑制剂格列苯脲和5-羟基酸可以阻断二氮嗪的这种保护作用。K+-ATP通道活化剂二氮嗪对于实验性大鼠的在体缺血再灌注损伤具有一定的保护作用。
【Objective】 To study the mechanism of lung ischemia-reperfusion injury and the protective effects of Diazoxide （KATP opener） on lung ischemia-reperfusion injury in vivo. 【Methods】 The model of ischemia-reperfusion （1h of ischemia and 30 mins of reperfusion） was established. Sixty male Sprague-Dawley（SD） rats weighting 260～330 g were randomly divided into five groups： sham group （control group, n=12）; ischemia-reperfusion group（I/R group, n=12）; Diazoxide group （n=12）; Diazoxide＋Glibenclamide group （n=12）and Diazoxide＋5-HD （n=12） group. We compared the wet to dry ratio of these five groups and also measured the lactate dehydrogenase （LDH） in the bronchoalveolar lavage fluid （BALF） after reperfusion. Alveolar fluid clearance （AFC） was estimated by the progressive increase in the albumin concentration after 30 mins of reperfusion. 【Results】 Lung W/I） ratio and LDH in BALF of Diazoxide group （5.59±0.34）% and （952.5±108.70） IU/L were significantly lower than those of I/R group （6.58±0.55）% and （1660±137.40） IU/L（P 〈 0.01）. AFC of Diazoxide group （6.72±0.97） % was much higher than that of I/R group （3.96±0.56）% （P 〈 0.01）. The effects of Diazoxide were blocked by KATP Channel antagonists 5-HD and Glibenclamide. 【Conclusions】 Diazoxide increased AFC of lung in vivo after reperfusion and decreased lung edema. It could protect effectively the injury of lung ischemia-reperfusion in vivo.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2006年第2期176-179,共4页
China Journal of Modern Medicine
