低分子肝素对脑缺血再灌注大鼠NF-κB、MPO活性的影响

目的探讨低分子肝素（Low molecular weight heparin，LMWH）对核转录因子-κB p65（NF-κB p65）和髓过氧化物酶（MPO）活性的影响。方法将Wistar大鼠135只，随机分为假手术组、缺血再灌注组（IR组）、LMWH治疗组，线栓法建立局灶性脑缺血再灌注模型。IR组于再灌注前5min尾静脉注射LMWH，1．5mg／kg。采用免疫组化法和生化法观察各组缺血90min再灌注3、6、12、24、48h点NF-κB p65表达、MPO活性变化，并进行脑含水量检测、TIC染色和HE染色观察脑梗死体积及病理形态学变化。结果①假手术组及IR组的未缺血侧大脑半球可见少量NF—κBp65表达于胞质，再灌注后NF-κB p65表达发生核移位，于胞核表达增加，再灌注12h达高峰；与IR组比较，LMWH治疗组能减少NF-κB p65的核移位（P〈0．05）；②再灌注12h后，MPO活性升高，于24h达到高峰；与IR组比较，LMWH治疗组能减少MPO活性（P〈0．05）；③与IR组比较，LMWH治疗组脑含水量较IR组减少，脑梗死体积较IR组缩小，差异有统计学意义（P〈0．05）；④LMWH治疗组脑组织缺血损伤病理学改变明显轻于IR组；⑤假手术组、IR组和LMWH治疗组凝血酶原时间（胛）和白陶土部分凝血活酶时间（KPTT）检测比较，差异无统计学意义（P〉0．05）。结论脑缺血再灌注损伤出现NF-xB活化和中性粒细胞浸润的炎性反应级联反应。LMWH对脑缺血再灌注损伤有保护作用，可能与减少NF-κB p65活化和减轻中性粒细胞浸润有关，且对凝血指标胛和KPTT无明显影响。

Effect of Low molecular weight heparin on NF-κB and MPO Activity of cerebral ischemia reperfusion injury in rats

Objective TO study effect of Low molecular weight heparin（LMWH） on NF-κB p65 and MPO of cerebral ischemia reperfusion injury in rats. Methods In this experiment, 135 Wistar rats were randomly divided into 3 groups, which were sham operated group, ischemia reperfusion group（ IR group）, LMWH treated group. The focal middle cerebral artery occlusion（MCAO） model was made by suture-occluded method. Rats were given LMWH by vena caudalis injection, 5 rain before reperfusion. After MCAO following different durations of reperfusion,we investigated the expression of NF-κBp65 with using immunohistochemistry and investigated the MPO activity in the ischemic territory. The brain water content was examined. HE staining and TIC staining was also investigated. Results ①The translocation of NF-κBp65 from cytoplasm to nucleus increased significantly after reperfusion, and peaked at 12 h of reperfusion . Compared with IR group, LMWH treated group reduced expression of NF-κBp65. ②MPO activity was started to significantly increased at 12 h and peaked at 24 h of reperfusion in the ischemic territory. Compared with IR group, LMWH treated group reduced MPO activity. ③Compared with IR group, LMWH treated group reduced the brain water content and cerebral infarction volume was lower than IR group （P 〈 0. 05 ）. ④The change of ischemic impairment in LMWH treated group was lighter than that of IR group. ⑤Compared with that of sham operated group, the prothrombin time（PT） and kaolin partial thromboplastin time （KFFF） of IR group and LMWH treated group have no difference. （ all P 〉 0.05 ）. Conclusion There is inflammation reaction of NF-κBp65 and neutrophils infiltration af- ter cerebral ischemia-reperfusion-injury. LMWH may reduced cerebral ischemia-reperfusion injure by decreasing the expression of NF-κBp65 and neutrophils infiltration, without affecting the clotting indices PT and KPTT.