化痰通络方对急性脑梗死大鼠溶栓后血脑屏障相关构成蛋白表达的影响  

Effect of Phlegm-Transforming Network Vessels-Freeing Formula on the Blood Brain Barrier-Related Protein Expression in Acute Cerebral Infarction Rats after Thrombolysis

作　　者：张玉莲[1] 周震[1] 宋宛珊[2] 樊晓靖[1] 张琳琳[1] 刘爽[1] 马妍[2] 

机构地区：[1]天津中医药大学第二附属医院 [2]天津中医药大学

出　　处：《中医杂志》2013年第24期2128-2131,2134,共5页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81072796)

摘　　要：目的探讨化痰通络方对急性脑梗死经重组组织纤溶酶原激活剂(rt-PA)溶栓后出血的可能作用机制。方法 240只SD大鼠随机分为假手术组、模型组、rt-PA组及化痰通络方低、中、高剂量组,采用自身栓子法制备大鼠大脑中动脉栓塞模型,化痰通络方低、中、高剂量组分别于血栓注入后3h一次性由尾静脉缓慢注入rt-PA(5.67mg/kg)进行溶栓治疗后给予化痰通络方浓缩液0.72g/kg、1.44g/kg、2.88g/kg灌胃;rt-PA组溶栓治疗后给予等量生理盐水灌胃;假手术组和模型组相同时间点给予等量生理盐水灌胃;各组每日灌胃2次,共7天。各组于实验6h、24h,72h、7天4个时相电镜观察各组大鼠大脑皮质缺血区内皮细胞微观形态,应用Western blot法检测大脑皮质咬合蛋白(occluding)、闭合蛋白(claudin-1)、胞浆附着蛋白(ZO-1)的表达。结果与假手术组比较,模型组大鼠在24h、72h时大脑皮质occluding、claudin-1、ZO-1蛋白表达下降(P<0.05);与模型组比较,化痰通络方高剂量组在6h、24h、72h时occluding、claudin-1蛋白表达明显升高(P<0.05),化痰通络方中剂量组在24h、72h时occluding蛋白表达升高(P<0.05);化痰通络方中、高剂量组在24h、72h时occluding蛋白表达高于rt-PA组(P<0.05);化痰通络方中剂量组在72h时claudin-1蛋白表达高于rt-PA组,24h时ZO-1蛋白表达高于rt-PA组(P<0.05)。结论化痰通络方可能通过改善大脑皮质内皮细胞微观形态,调控微血管内皮细胞构成蛋白occluding、claudin-1、ZO-1蛋白的表达,进而保护血脑屏障完整性。Objective To study the possible mechanism of Phlegm-Transforming Network Vessels-Freeing Formula in preventing and treating bleeding after thrombolytic therapy with recombinant tissue plasminogen activator（rt-PA）in acute cerebral infarction.Methods Totally 240 SD rats were randomized into the sham operation group,model group,rt-PA group and low-dose,middle-dose,and high-dose Chinese medicinal groups.The middle cerebral artery occlusion models were established with self-embolism.The low-dose,middle-dose,and high-dose Chinese medicinal groups were injected 5.67mg/kg of rt-PA through the tail vein 3 hours after thrombus injection.After thrombolytic therapy,the low-dose,middle-dose and high-dose Chinese medicinal groups were gavaged with 0.72g/kg,1.44g/kg and 2.88g/kg concentrated solution of PhlegmTransforming Network Vessels-Freeing Formula,respectively.The rt-PA group was gavaged with equal amount of normal saline after thrombolytic therapy.The sham operation group and model group were gavaged with equal amount of normal saline at the same time point.Each group was given intragastric administration twice daily for 7 days.The morphology of endothelial cells in ischemic region of cerebral cortex was observed with electron microscopy at the 6th,24th and 72nd hour and on the 7th day of experiment.The expressions of occluding,claudin-1 and ZO-1 proteins were detected with Western blotting.Results Comparing with the sham operation group,the expressions of occluding,claudin-1 and ZO-1 proteins were significantly decreased at the 24th and 72nd hour and on the 7th day of experiment in the model group（P〈0.05）.Comparing with the model group,the expressions of occluding and claudin-1 proteins were significantly increased at the 6th,24th and 72nd hour of experiment in the high-dose Chinese medicinal group（P〈0.05）,and the expression of occluding protein was significantly increased at the 24th and 72nd hour of experiment in the middle-dose Chinese medicinal group（P〈0.05）.Comparing with the rt-PA group,the e

关 键 词：化痰通络法方 急性脑梗死 溶栓 血脑屏障 结构蛋白 

分 类 号：R285.5[医药卫生—中药学]