Zhou Tong, Chen Jin-Lian, Song Wei, Wang Feng, Zhang Ming-Jun, Ni Pei-Hua, Geng Jian-Guo
Department of Nephrology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025,China.
World J Gastroenterol. 2002 Oct;8(5):897-900. doi: 10.3748/wjg.v8.i5.897.
To investigate the effect of N-desulfated heparin on hepatic/renal ischemia and reperfusion injury in rats.
Using rat models of 60 minutes hepatic or renal ischemia followed by 1 h,3 h,6 h and 24 h 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 12 mg/kg at 5 minutes before reperfusion. P-selectin expression was detected in hepatic/renal tissues with immunohistochemistry method.
P-selectin expression, serum ALT, AST, BUN and Cr levels were significantly increased during 60 minute ischemia and 1 h, 3 h, 6 h and 24 h reperfusion,while the increment was significantly inhibited,and hepatic/renal pathology observed by light microscopy was remarkably improved by treatment with the N-desulfated heparin. Furthermore,the heparin was found no effects on PT and KPTT.
P-selectin might mediate neutrophil infiltration and contribute to hepatic/renal ischemia and reperfusion. The N-desulfated heparin might prevent hepatic/renal damage induced by ischemia and reperfusion injury without significant anticoagulant activity.
探讨去硫酸化肝素对大鼠肝/肾缺血再灌注损伤的影响。
采用大鼠肝或肾缺血60分钟后再灌注1小时、3小时、6小时和24小时的模型，动物随机分为以下几组：假手术对照组、仅接受生理盐水的缺血组以及在再灌注前5分钟接受12mg/kg去硫酸化肝素的治疗组。采用免疫组织化学方法检测肝/肾组织中P-选择素的表达。
在60分钟缺血及1小时、3小时、6小时和24小时再灌注期间，P-选择素表达、血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、血尿素氮（BUN）和肌酐（Cr）水平显著升高，而去硫酸化肝素治疗可显著抑制其升高，并且光镜下观察到的肝/肾病理改变明显改善。此外，发现该肝素对凝血酶原时间（PT）和活化部分凝血活酶时间（KPTT）无影响。
P-选择素可能介导中性粒细胞浸润并导致肝/肾缺血再灌注损伤。去硫酸化肝素可能预防缺血再灌注损伤诱导的肝/肾损伤，且无明显抗凝活性。
