N-去硫酸肝素对肾缺血再灌注损伤防治作用的研究

Effects of Ndesulfated heparin on renal ischemiareperfusion injury in rats

目的 :研究 N去硫酸肝素对大鼠肾缺血再灌注损伤的防治作用。方法 :建立肾缺血再灌注损伤大鼠模型 ,实验动物随机分为正常对照组和 N 去硫酸肝素治疗及非治疗组。观察大鼠治疗前后肾组织中 P 选择素表达、组织病理学与肾功能的改变 ,以及凝血指标〔包括凝血酶原时间 (PT)和部分激活凝血时间 (KPTT)〕的变化。结果 :缺血再灌注后大鼠肾脏 P 选择素表达增高 ,出现明显组织病理学改变 ,血清尿素氮 (BUN)、肌酐(Cr)水平明显升高〔分别为 (14.5 4± 0 .6 7) mm ol/ L 和 (10 2 .12± 4.76 ) μmol/ L〕;N 去硫酸肝素治疗组肾脏组织中 P选择素表达受抑 (未出现棕黄色颗粒 ) ,病理学改变与肾功能损害减轻 ,且对 PT和 KPTT无明显影响。结论 :N去硫酸肝素对肾缺血再灌注损伤具有防治作用 ,且对凝血指标 PT和 KPTT无明显影响。

Objective:To investigate the effects of Ndesulfated heparin on renal ischemiareperfusion injury in rats.Methods:Using a rat model of 60 minutes renal ischemia followed by 1,3,6 and 24 hours reperfusion,animals were randomly divided into following groups:the shamoperated control,ischemic group receiving only normal saline,and treatment group receiving Ndesulfated heparin at a dose of 12 mg/kg at 5 minutes before reperfusion.Pselectin expression was observed in renal tissues with immunohistochemistry method.Results: Pselectin expression,blood urea nitrogen(BUN) and creatinine(Cr) levels were significantly increased after 60 minutes ischemia and 1,3,6 and 24 hours reperfusion.However the expression was significantly inhibited,and renal pathology observed by light microscopy was remarkably attenuated with the treatment with Ndesulfated heparin.On the other hand,Ndesul fated heparin was found to have no effects on prothrombin time(PT) and kadin partial thromboplastin time(KPTT).Conclusions:Our results suggest that this Ndesulfated heparin can be of therapeutic potential for renal damage induced by local ischemiareperfusion injury without significant anticoagulant activity.