降纤酶的不同给药途径和时间对大鼠局灶性脑缺血的影响

目的探讨不同的给药途径下降纤酶去纤作用及其对局灶性脑缺血的影响 ,并分析静脉用药的治疗时间窗问题。方法采用雄性Wistar大鼠共 178只 ,其中 15 4只用线栓法制备局灶性脑缺血模型 ,被随机分为假手术组、降纤酶治疗组及生理盐水对照组 ,根据给药途径的不同每组又分为静脉给药和腹腔给药两个亚组。静脉给药组根据给药时间的不同又分为 0 5、3、6、9、12h5个组。给予神经功能评分 ,脑标本用TTC染色以测量梗死灶体积 ,HE染色以观察病理改变。另 2 4只大鼠分静脉及腹腔两种给药途径注射降纤酶 ,并在注药后 0 5、3、6、12、2 4h采血 ,测定纤维蛋白原浓度。对比分析降纤酶不同给药途径及不同纤维蛋白原水平对疗效的影响及治疗时间窗的问题。结果静脉给药组的纤维蛋白原下降最快 ,3h下降至最低值 ;腹腔给药组的纤维蛋白原平缓下降 ,6h下降至最低。缺血后 0 5、3h经静脉给药治疗组大鼠的神经功能评分改善、脑梗死体积最小 ,与降纤酶腹腔给药组、生理盐水对照组相比均有显著差异 (P <0 0 5 ) ;降纤酶腹腔给药组与生理盐水对照组相比仅神经功能评分改善 ,梗死灶体积无显著差异 (P >0 0 5 )。缺血 6、9、12h静脉给药组大鼠的神经功能评分、脑梗死体积与对照组比较均无明显差异 (P >0 0 5 )。结论缺血早期静

Experimental study of the therapeutic effectiveness of defibrase on treating acute cerebral ischemia and the effectiveness in different administrated ways

ObjectiveTo investigate the intensity of degrading plasma fibrinogen(FIB) and the therapeutic effectiveness of defibrase on treating cerebral ischemia by different administrated ways. MethodsIntraluminal suture method was used to develop reversible middle cerebral artery occlusion (MACO). 154 healthy male Wistar rats were randomized into 2 groups. The rats in intravenous treatment group were injected defibrase intravenously at 0.5,3,6,9,12hours after MACO,while the rats in coeliac treatment group were injected defibrase by abdominocentesis. Meanwhile the control group received normal saline. All rats were killed at 24 hours after MCAO. The thrombus in middle cerebral artery (MCA) and cerebral infarction were examined microscopically in HE stained sections. Infarction volume was measured by using 2,3,5-triphenyltetrazolium chloride staining. 24 rats were selected randomly and injected defibrase by intravenous injection and abdominocentesis. Plasma FIB was measured before and after injection 1,3,6,12,24h by intravenous haemospasia. ResultsPlasma FIB was significantly reduced in intravenous treatment group, and it was lowerest in 3h after intravenous treatment.Clinical Neurological Deficits Scale and infarction volume was significantly reduced in intravenous treatment group than saline control group and coeliac treatment group.There was improvement in Clinical Neurological Deficits Scale in coeliac treatment group compared with that of saline control group, but there was no statistically significant differences at infarction volume.Clinical Neurological Deficits Scale and infarction volume was statistically significant differences in intravenous treatment group at 0.5,3 hours after MCAO. There were no statistically significant differences in intravenous treatment group at 6, 9,12 hours after MCAO.Conclusions Defibrase can reduce the infarction volume in cerebral ischemia early stage.