The Release Effect Of Sildenafil Citrate On Cerebral Vasospasm After Subarachnoid Hemorrhage Of The Adult Rat

Objective:To establish the rat model of subarachnoidal hemorrhage by double injections of blood into cistern magna. To probe into the release effect of sildenafil citrate(SC) on cerebral vasospasm in subarachnoidal hemorrhage(SAH) model rats by detecting the expression of cGMP, endothelin-1(ET-1) in plasma and endothelin receptor A(ETR-A) in basilar artery in different periods of time.Materials and Methods: Animal models of SAH was established by double injections of blood into cistern magna method. 120 Sprague-Dawley(SD) rats were randomly divided into five groups: group A(blank),group-only do normal feeding and without any other treatments. B(sham operation ),group-to inject normal saline(NS) into cistern magna then feed them in a normal way. C(SAH),group-To inject autologous femoral artery blood into cistern magna then feed them in a normal way. D(NS)-to treat SAH model rats with 2mL NS once a day. E(SAH+SC)-To treat SAH model rats with 2ml SC once a day(concentration 1mg/ml ).Then each group was divided into four subgroups according to different post-operation time. The plasma level of cGMP and ET-1 was detected after 1 day ,4days,7days,14days for each subgroup respectively by doing amputations of tail to get blood. Then, the brain tissues were gotten by killing the rats for the following HE staining and immunohistochemistry staining. The diameter and thickness of the basilar artery were observed with IPP image analyzing system. The expression of ETA-R on basilar artery was examined with immunohistochemistry. SPSS13.0 software was adopted in the analysis of the experimental results. Results:HE staining of the basilar artery showed no significant changes in group A and B, while the convulsion of the basilar artery could be observed in group C and D with a smaller diameter and thicker blood vessel wall. The cerebral vasospasm effect could be obviously seen at the first day after SAH, and reached its peak point at 7days then got eased at 14 days. Compared with group C and D, the convulsion of basilar artery in group E was milder. The plasma level of cGMP in group E was lower than that of group A and B, but higher than that of group C and D. The ET-1 level in group C,D and E was higher than that of group A and B. And no significant differences exist between group C,D and E. The immunohistochemistry staining showed more expression of ETA-R in group E than in group A and B, but less than group C and D. And in the subgroups of C,D and E, ETA-R had the most expression at 7 days after SAH.Conclusions: "Autoblood injection into cisterna magna" method could be applied to establish the SAH model in rats. The convulsion of the basilar artery began at 1 day after SAH, reached its peak effect at 7 days and eased at 14 days. After SAH , the expression of cGMP in plasma decreased while the plasma level of ET-1 and the expression of ETA-R on basilar artery increased. Sildenafil citrate reduces the convulsion of the basilar artery after SAH.