蛛网膜下腔出血模型大鼠基底动脉蛋白酶激活受体-1 的表达

目的探讨蛛网膜下腔出血（SAH）模型大鼠基底动脉PAR1表达与脑血管痉挛（CVS）之间的关系。方法7周龄清洁级SD
大鼠24只，随机数字表法分为正常组、SAH 3 d组、SAH 5 d组、SAH 7 d组，采取二次枕大池注血法建立大鼠SAH模型，观察动
物行为学改变，SAH模型大鼠按照分组于术后3、5、7 d 分别灌杀动物，显微镜下观察基底动脉组织学形态，并以Image-Pro
Plus6.0图像分析软件测量基底动脉管腔横截面积，免疫组化检测基底动脉标本PAR1表达。结果SAH制模术后参照Endo 4分
制方法行神经功能评分SAH 3 d组中2分2只（33.3%），3分4只（66.7%）；SAH 5 d组中1分3只（50%），2分3只（50%）；SAH 7 d
组中1分4只（66.7%），2分2只（33.3%）；正常组均为1分。CVS观察：正常组无痉挛，SAH 3 d组出现基底动脉痉挛，SAH 5 d组
基底动脉稍舒张，SAH 7 d组痉挛程度较3 d组加重，统计分析显示四组之间的差异有统计学意义（P<0.05），组间两两比较差异
有统计学意义（P<0.05）。PAR1免疫组织化学结果分析：正常组未见明显表达，SAH模型制作后后3、5、7 d组基底动脉PAR1有
阳性表达。统计分析显示四组间PAR1平均光密度差异有统计学意义（P<0.01），组间两两比较显示正常组与SAH 3 d组、正常
组与SAH 5 d组、正常组与SAH 7 d组、SAH 3 d组与SAH 5 d组、SAH 3 d组与SAH 7 d组差异具有统计学意义（P<0.01），SAH
5 d组与SAH 7 d组相比差异具无统计学意义（P>0.05）。Pearson相关分析显示PAR1平均光密度与SAH后基底动脉横截面积
之间存在负相关（r为-0.779，P<0.01）。结论本实验中SAH大鼠模型基底动脉PAR1表达上调，并与CVS严重程度呈负相关关
系，凝血酶受体PAR1在CVS发生发展过程中表达上调，提示凝血酶参与了SAH后CVS的病理过程。

Expression of protease-activated receptor 1 in the basilar artery of rats following subarachnoid hemorrhage

Objective To assess the relationship between protease-activated receptor 1 (PAR1) expression in the basilar artery
and cerebral vasospasm (CVS) in a rat model of subarachnoid hemorrhage (SAH). Methods Twenty-four SD rats were
randomized into normal control group, SAH 3-days group, SAH 5-days group and SAH 7-days group. Rat models of SAH
were established by two injections of blood into the cisterna magna and the behavioral changes of the rats were observed. The
basilar arteries were taken at 3, 5, or 7 days following the modeling for measuring the cross-sectional area of the basilar artery
and for immunohistochemical detection of PAR1 expression. Results The SAH model rats, especially those in SAH 3-days
group, presented with obvious neurological deficits, which was not found in the normal control group. CVS was not observed
in the normal control group but occurred in the SAH model rats, which showed reduced cross-sectional area of the basilar
artery and worsening spasm over time. The expression level of PAR1 tended to increase gradually in SAH 3-days, SAH 5-days
and SAH 7-days groups. Pearson correlation analysis showed an inverse correlation between the expression of PAR1 and the
cross-sectional area of the basilar artery (r=-0.779, P<0.01). Conclusions The expression of PAR1 increases significantly in rat
basilar artery wall following SAH in positive correlation with the severity of CVS, suggesting the role of thrombin in the
pathological process of CVS after SAH.