Roles of hirudin in protease activated receptor 1 expression changes in basal artery of rat subarachnoid hemorrhage models

Abstract

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 Sprague 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 cisterna 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 7th 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 significantly smaller 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. Key words: Subarachnoid hemorrhage; Cerebral vasospasm; Thrombin; Hirudin; Protease activated receptor 1