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

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.