摘要
目的探讨凝血酶抑制剂水蛭素对蛛网膜下腔出血(SAH)模型大鼠血管痉挛的影响及其作用机制。方法7周龄清洁级SD大鼠36只按照随机数字表法分为3组:对照组(12只1、SAH组(12只)、SAH+水蛭素组(12只),后两组采用二次注血法制作成SAH模型,SAH+水蛭素组同时注入水蛭索200U/mL血液。观察各组大鼠的行为学改变,并于术后7d在显微镜下观察基底动脉HE染色组织学形态,Image-ProPlus6.0图像分析软件测量基底动脉管腔横截面积,免疫组化染色检测基底动脉标本蛋白酶激活受体1(PAR-1)表达。结果基底动脉HE染色可见对照组血管管腔最大,管壁薄,内膜光滑无褶皱;SAH组基底动脉管腔窄,管壁厚,内皮褶皱;SAH+水蛭素组管壁及管径变化介于对照组与SAH组之间。并且SAH+水蛭素组管腔横截面积较SAH组明显大,SAH组、SAH+水蛭素组管腔横截面积较对照组明显小,差异均有统计学意义(P〈0.05)。免疫组化染色结果显示SAH组和SAH+水蛭素组基底动脉血管内皮细胞及平滑肌细胞的胞浆及胞核中均可见PAR-1阳性表达,其中SAH组表达较强,SAH+水蛭素组表达较弱,并且SAH+水蛭素组PARl吸光度值较SAH组明显低,SAH+水蛭素组、SAH组PAR-1吸光度值较对照组明显高,差异均有统计学意义(P〈0.05)。结论水蛭素注入蛛网膜下腔后可降低PAR-1的表达,能缓解基底动脉血管痉挛表现,提示凝血酶在SAH模型大鼠脑血管痉挛的发生发展过程中发挥了重要作用。
Objective To discuss the influence of direct thrombin inhibitor hirudin in the expression ofprotease activated receptor 1 (PAR-1) in basilar artery of the rat model with subarachnoid hemorrhage (SAH). Methods Thirty-six Spragne Dawley rats (7 weeks old, clearanimal) were divided into 3 groups randomly: control group (n=12), SAH group (n=12) and SAH+hirudin treatment group (n=12). The rat models of SAH in the later two groups were induced by twice injection blood into the cistema magna; rats in the SAH+hirudin treatment group also accepted blood with 200 U/mL hirudin. Animal behavior changes were recorded. Rats of different groups were killed on the 7~ d of model making, and samples of basilar artery were performed HE staining for histological observation under microscope; vascular changes of cross-sectional area were measured by Image-Pro Plus6.0 imaging analysis software; and PAR-1 expression was detected by immunohistochemistry. Results Larger vascular lumen, thinner wall, smoother lining and no fold in the basal artery of control group were found as compared with thick wall, narrow lumen and endothelial fold in SAH model rats; the changes of basal artery in SAH+hirudin treatment group enjoyed in the medium ranking. The vascular changes of cross-sectional area in the SAH+hirudin treatment group were more obvious than those in the SAH group (P〈0.05); the cross-sectional area in the SAH+hirudin treatment group and SAH group was significantlysmaller than that in the control group (P〈0.05). The immunohistochemistry results showed there was no PAR-1 expression in the rats of control group, and PAR-1 positively expressed in the basilar artery of rats in the SAH group and weakly expressed in that of SAH+hirudin treatment group. The PAR-1 absorbance value in the SAH+hirudin treatment group and SAH group was significantly higher than that in the control group; and that in the SAH+hirudin treatment group was significantly lower than that in the SAH group (P〈0.05). Conclusion Hirudin can reduce PAR-1 expression in the basilar artery of SAH rat models and relieve artery vasospasm, which indicates that thrombin may play important roles in the pathological process of cerebral vasospasm after SAH.
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2013年第11期1123-1127,共5页
Chinese Journal of Neuromedicine
基金
海南省卫生厅科研课题(琼卫2010-64)