家兔脑梗死模型血浆血管内皮生长因子和内皮素表达与降纤酶的干预实验

Expressions of plasma vascular endothelial growth factor and endothelin in rabbit models of cerebral infarction and the intervention of defibrinogenase

目的:观察降纤酶对家兔脑梗死模型动脉血浆血管内皮生长因子和内皮素1水平的影响,并与低分子肝素钠的效果相比较。方法:实验于2003-09／2004-04在山东大学动物实验室进行。取家兔 40只,随机分为正常对照组,空白对照组,低分子肝素钠组和降纤酶组 4组,每组10只。除正常组外,其他3组家兔食用高糖高脂饲料10 d, 制备高糖高脂血症模型,模型成功后应用自体血栓栓塞方法制备家兔脑梗死模型。脑梗死模型制备后2 h低分子肝素钠组腹腔内注射低分子肝素钠20 U／kg,降纤酶组静脉推注降纤酶0．1 U／kg,1次／d,连续7 d, 其他两组不给药。于高糖高脂血症模型造模前后、给药前及给药第8天分别4次抽血检测动脉血浆中血脂、血糖、血管内皮生长因子和内皮素的变化。结果:40只兔全部进入结果分析。①内皮素1水平:空白对照组、低分子肝素钠组和降纤酶组高脂高糖血症模型制备后明显高于造模前(P<0．01); 脑梗死模型2h后各组均高于梗死前和正常对照组(P<0．01);治疗后仅降纤酶组的内皮素1水平低于治疗前和空白对照组[(23.8±31．8),(19．3±2.8), (29.7±3.4)ng/L,P<0．01]。②血管内皮生长因子水平:空白对照组、低分子肝素钠组和降纤酶组高脂高糖血症模型制备后明显高于造模前(P<0．01);脑梗死模型2 h后各组均高于梗死前和正常对照组(P<0．01);治疗后仅降纤酶组的血管内皮生长因子水平高于治疗前和空白对照组[(76．2±8．1), (64.6±5．6),(62.2±5．8)ng/L,P<0．01]。③血脂、血糖:空白对照组、低分子肝素钠组和降纤酶组高脂高糖血症模型制备后明显高于造模前(P<0．01); 脑梗死模型2 h后及给予治疗1周后检测的三酰甘油、胆固醇和葡萄糖与梗死前比较无显著差异(P>0．05)。结论:脑梗死可引起血浆血管内皮生长因子和内皮素1浓度升高,降纤酶可能通过影响这两种生物分子的生物学效应而发挥治疗作用,而低分子肝素钠无此作用。

AIM：To observe the effect of defibrinogenase on the levels of vascular endothelial growth factor （VEGF） and endothelin in the arterial plasma of rabbit models of cerebral ischemia model, and compare the effects with those of low dose heparin. METHODS：The experiment was carried out in the animal laboratory of Shandong University between September 2003 and April 2004.Forty rabbits were randomly divided into 4 groups with 10 rabbits in each group： normal control group,blank control group,low dose heparin group and defibinogenase group.Except the normal control group,the rabbits in the other three groups were fed with food of high lipids and glucose for 10 days to made models of high blood lipids and glucose.After the success of the models, the rabbit models of cerebral infarction were made by means of autologous thromboembolia. At 2 hours after the model establishment, the rabbits in the low dose heparin group and defibinogenase group were treated with intraperitoneal injection of low dose heparin （20 U/kg） and intravenous injection of defibinogenase （0.1 U/kg）, once a day for 7 continuous days, and no administration was given to the rabbits in the other two groups. The blood samples were extracted before and after the establishment of high blood lipids and glucose model and before administration and on the 8^th day after administration to detect the changes of blood lipids, blood glucose, VEGF and endothelin in arterial plasma. RESULTS：All the 40 rabbits were involved in the analysis of results.①Endothelin-1 level：It was obviously higher after the establishment of high blood lipids and glucose model than before the establishment in the blank control group, low dose heparin group and defibinogenase group （P 〈 0.01）. The endothelin-1 level at 2 hours after model establishment of cerebral infarction was higher than that before infarction and that in the normal control group （P 〈 0.01）. After treatment, only the endothelin-1 level in the defibrinogenase group was lower than that before treatment and that in the normal control group [（23.8±31.8）, （19.3±2.8）, （29.7±3.4） ng/L, P 〈 0.01]. ②VEGF level：It was obviously higher after the establishment of high blood lipids and glucose model than before the establishment in the blank control group,low dose heparin group and defibinogenase group （P 〈 0.01）.The VEGF level at 2 hours after model establishment of cerebral infarction was higher than that before infarction and that in the normal control group （P〈 0.01）. After treatment, only the VEGF level in the defibrinogenase group was lower than that before treatment and that in the normal control group [（76.2±8.1）, （64.60±5.6）,（62.2±5.8） ng/L,P 〈 0.01]. ③Blood lipids and blood glucose： The blood lipids and blood glucose were obviously higher after the establishment of high blood lipids and glucose model than before the establishment in the blank control groul, low dose heparin group and defibinogenase group （P 〈 0.01）. The levels of triglyeeride, cholesterol and glucose at 2 hours after cerebral infaretion and 1 week after treatment were insignificantly different from those before infarction （P 〉 0.05）. CONCLUSION：Cerebral infarction can cause the increases of plasma VEGF and endothelin-1,and defibrinogenase can play a therapeutic role through affecting the biological effects of the two kinds of biological molecules, but low dose heparin do no have the action.