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山东大学学报（医学版）

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超时间窗溶栓治疗对急性脑梗死体积、微血管密度及黏附因子表达的影响

林艳1，刘金之1，刘杰1，杨倩倩2，司志华1，徐珊1，王爱华1   

  1. 1.山东大学附属千佛山医院神经内科， 山东 济南 250014；
    2.江苏省苏州市广济医院神经内科， 江苏 苏州 215008
  • 收稿日期:2014-01-19 出版日期:2014-05-10 发布日期:2014-05-10
  • 通讯作者: 王爱华 E-mail: wangah_0052@sina.com
  • 基金资助:
    山东省科技发展计划项目(2011GGB14095)

Effects of thrombolytic therapy with broadened therapeutic window on infarct volume, microvessel density and adherence factors in acute cerebral infarction

LIN Yan1, LIU Jinzhi1, LIU Jie1, YANG Qianqian2, SI Zhihua1, XU Shan1, WANG Aihua1   

  1. 1. Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China;
    2. Department of Neurology, Suzhou Guangji Hospital, Suzhou 215008, Jiangsu, China
  • Received:2014-01-19 Online:2014-05-10 Published:2014-05-10

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摘要： 目的  观察超时间窗溶栓治疗对急性脑梗死体积、微血管密度(MVD)及黏附因子(ICAM-1、VCAM-1)表达的影响。方法  SD大鼠216只随机分为对照组、梗死组、4.5h溶栓组和6h溶栓组，每组动物随机分为3个亚组，分别于1、3、7d时取脑。采用TTC染色观察脑梗死面积，免疫组化染色观察梗死灶周围微血管密度，实时定量PCR法检测梗死灶周边ICAM-1、VCAM-1 mRNA表达量。结果  4.5h和6h溶栓组各时间点脑梗死体积较梗死组明显缩小(P均<0.01)，随着溶栓时间延长，梗死体积逐渐增大，两者差异有统计学意义(P<0.05)；脑梗死3d，4.5h和6h溶栓组MVD表达较梗死组增加(P均<0.05)，7d时明显增加(P均<0.01)。4.5h和6h溶栓组MVD随溶栓时间延长MVD逐渐增加，7d较3d增加明显(P<0.05)，但两溶栓组在1、3、7d时MVD差异无统计学意义(P>0.05)；梗死组、4.5h和6h溶栓组ICAM-1、VCAM-1 mRNA表达量1d开始升高(P<0.01)，3d达高峰(P<0.01)，7d仍高于对照组(P<0.01)，4.5h和6h溶栓组各时间点ICAM-1、VCAM-1 mRNA表达量较梗死组明显降低(P均<0.05)，随着溶栓时间延长，ICAM-1、VCAM-1 mRNA表达量均进一步升高，两组差异有统计学意义(P<0.05)。结论  超时间窗溶栓可降低急性梗死灶体积，增加梗死灶周围微血管密度，降低免疫黏附因子的表达，为临床脑梗死超时间窗的溶栓治疗提供可靠的理论依据。

关键词: 脑梗死, 时间窗, 微血管密度, 黏附因子, 溶栓

Abstract: Objective  To explore the effect of recombinant tissue plasminogen activator(r-tPA) thrombolytic therapy with broadened therapeutic window on the cerebral infarct volume, microvessel density (MVD), and expression of adherence factors (ICAM-1 and VCAM-1) in acute cerebral infarction. Methods  A total of 216 SD rats were randomly divided into the control group, stroke group, rtPA 4.5h group and rtPA 6h group. Each group was randomly divided into three subgroups, and brains were drawn from the animals in each subgroup on the 1st, 3rd and 7th day. TTC staining was employed to observe cerebral infarct volume, immunohistochemical staining was used to observe MVD around ischemic core, and real time-PCR was used to detect the expression quantity of ICAM-1 and VCAM-1 mRNA around cerebral infarcts. Results  Compared with the stroke group, the cerebral infarct volume was obviously reduced in the rtPA 4.5h group and rtPA 6h group at each time point (P<0.01). The cerebral infarct volume increased with the thrombolysis time, with statistical differences between the rtPA 4.5h group and rtPA 6h group(P<0.05). MVD was higher in the rtPA 4.5h and rtPA 6h groups compared with the stroke group on the 3rd day (P<0.05), which was significantly higher on the 7th day (P<0.01). MVD of the rtPA 4.5h group and rtPA 6h group increased with time, and the increase was more significant on the 7th day than on the 3rd day (P<0.05). No change of MVD were found between rtPA 4.5h group and rtPA 6h group on the 1st, 3rd and 7th day (P>0.05). The ICAM-1 and VCAM-1 mRNA expressions of stroke, rtPA 4.5h and rtPA 6h groups started to elevate (P<0.01) on the 1st day after thrombolysis, which reached peak on the 3rd day (P<0.01), and remained significantly elevated on the 7th day (P<0.01). Compared to the stroke group, the ICAM-1 and VCAM-1 mRNA expressions of rtPA 4.5h group and rtPA 6h group were lower at each time point (P<0.05). As the thrombolysis time extended, the ICAM-1 and VCAM-1 mRNA expressions of rtPA 4.5h and rtPA 6h groups increased, with statistical differences between them(P<0.05). Conclusion  The thrombolysis therapy of broadened time window could reduce the infarct volume, increase the microvessel density and inhibit the expression of immune adherence factors, which offers a reliable theoretical basis for the thrombolytic therapy of stroke.

Key words: Cerebral infarction, Time window, Thrombolysis, Microvessel density, Adherence factors

中图分类号: 

  • R743.3
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