N-去硫酸肝素对肝和肾缺血-再灌流损伤防治作用的研究  

The effects of N-desulbated heparin on hepatic and renal ischemia and reperfusion injury

作　　者：周同[1] 陈金联[2] 宋巍[1] 王锋[1] 张明钧[1] 张韶瑜[1] 陈楠[1] 耿建国[3] 

机构地区：[1]上海第二医科大学附属瑞金医院肾内科,200025 [2]上海市第六人民医院消化科 [3]中科院生物化学与细胞生物学研究所

出　　处：《中华急诊医学杂志》2002年第5期310-313,共4页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金 (3 9970 3 40 );卫生部科研基金(98 2 2 83 )

摘　　要：目的　探讨N -去硫酸肝素对肝和肾缺血 再灌流损伤的防治作用。方法　分别建立大鼠肝及肾缺血 再灌流损伤模型 ,观察和比较经N 去硫酸肝素处理前后大鼠肝、肾组织P 选择素表达 ,组织病理学改变及肝、肾功能变化 ,以及对凝血指标 (PT和KPTT)的影响。结果　肝、肾缺血再灌流后 ,大鼠肝、肾组织内P -选择素广泛表达 ,出现明显的组织病理学改变及肝、肾功能损伤。经给予N -去硫酸肝素处理后 ,肝、肾组织P -选择素表达受到抑制 ,组织病理学改变减轻 ,肝、肾功能得到改善。进一步发现N -去硫酸肝素对PT和KTPP无明显影响。结论　N -去硫酸肝素可能通过间接抑制P -选择素作用 ,而对肝和肾缺血 -再灌流损伤起到防治效果 。Objective To investigate the effect of N-Desulfated heparin on hepatic/renal ischemia and reperfusion injury.Methods Using rat models of 60 minutes hepatic or renal ischemia followed by 1h,3h,6h and 24h reperfusion,animals were randomly divided into following groups,the sham-operated controls,ischemic group receiving only normal saline,and treated group receiving N-desulfated heparin at a dose of 12mg/kg at 5 minutes before reperfusion.P-selectin expression was detected in hepatic/renal tissues with immunohistochemistry method.Results P-selectin expression,serum ALT,AST,BUN and Cr levels were significantly increased during 60 minute ischemia and 1h,3h,6h and 24h reperfusion,while the increment was significantly suppressed,and hepatic/renal pathology observed by light microscopy was remarkably improved by treatment with the N-desulfated heparin.Furthermore,the heparin was found to have no effects on PT and KPTT.Conclusion The results suggest that N-desulfated heparin can be of therapeutic potential for hepatic/renal damage induced by ischemia and reperfusion injury without significant anticoagulant activity.

关 键 词：N-去硫酸肝素 肾缺血 再灌流损伤 防治 肝缺血 

分 类 号：R965[医药卫生—药理学]