大黄苷元联合溶栓对血栓栓塞性脑缺血大鼠微血管基底膜损伤的保护作用

Effects of rhubarb aglycone combined with thrombolysis on brain microvascular basement membrane impairment in rats with thrombus-occluded cerebral ischemia

目的:从大黄苷元联合尿激酶溶栓对脑缺血大鼠脑组织IgG,IV型胶原(CoLIV)和层粘蛋白(LN)变化的影响方面探讨其对脑缺血微血管基底膜损伤的保护作用。方法:大鼠随机分组,制备血栓栓塞性脑缺血动物模型,大鼠分别于缺血后3,6,9 h经导管由区域动脉溶栓;动脉给药后24 h,观察大鼠死亡率和脑组织颅内出血率,测定脑组织IgG,CoLIV和LN。结果:脑缺血9 h溶栓可引起大鼠死亡率和脑出血率增高,联合用药可使其降低。模型6 h和9 h组大鼠脑组织IgG水平增高、CoLIV和LN表达降低;各用药9 h组较模型组IgG降低、CoLIV和LN表达增强;联合用药9 h组分别较两单一用药组IgG降低、CoLIV和LN表达增强。结论:脑缺血延迟溶栓可造成脑微血管基底膜损伤,引起颅内出血率和死亡率增高;大黄苷元联合溶栓对微血管基底膜损伤具有保护作用,可降低溶栓后的颅内出血率和死亡率。

Objective： To explore the protective effects of rhubarb aglycone combined with urokinase（UK）thrombolysis on brain microvascular basement membrane impairment in rats with thrombus-occluded cerebral ischemia by regulating the expression of IgG,CoLIV and LN in rats brain,by which the level of injury of brain microvascular basement membrane could be detected.Method： Rats were randomly divided into sham-operated,model,thrombolysis,rhubarb aglycone and combination（rhubarb aglycone combined with thrombolysis） groups.Moreover,rats in model,thrombolysis,rhubarb aglycone and combination groups were randomly divided into 3,6,and 9 h groups respectively.Model of thrombus-occluded cerebral ischemia was duplicated by using the combination of rats′ auto-thrombus with inserting the nylon thread.Rats were administrated with thrombolysis therapy through artery at 3,6,and 9 h after cerebral ischemia.At 24 h of administration through artery,intracranial hemorrhage ratio（ICHR） and mortality of rats were observed,and then the brain of rats was taken.In the study,expression of IgG,CoLIV and LN in rats brain were measured.Result： Thrombolysis at 9 h of cerebral ischemia made rats mortality and BHR increase,administration of combined therapy could make them decrease.Expression of IgG level in rats brain of 9 h and 6 h model groups increased,while CoLIV and LN expression decreased significantly.In each administration 9 h group,IgG level was lower,and CoLIV and LN were higher,such changes appeared significantly in rhubarb aglycone and association groups.Conclusion： Brain microvascular basement membrane impairment could be caused by the therapy of delayed thrombolysis,which made the mortality and BHR increase.Rhubarb aglycone combined with the therapy of thrombolysis could perform the protective effects on brain microvascular basement membrane and then decrease the ICHR and mortality caused by thrombolysis after cerebral ischemia.