| OBJECTIVE: To observe the effect of simvastatin on delayed cerebral vasospasm (DCVS), endothelial Nitric Oxide synthase(eNOS) and Tumor Necrosis Factor-alpha(TNF-α) in rat model of subarachnoid hemorrhage (SAH), and determine whether simvastatin could attenuate DCVS and explore the possible mechanism.METHODES: Thirty Sprague Dawley (SD) rats, half of which are male, were divided into three groups randomly (n =10). Shamed-injection group: Only cistema magna puncture was done with no injection of blood;SAH group: The double hemorrhage model of subarachnoid hemorrhage in rats were made by injecting autologous arterial blood (0.8 ml/kg) into the cistema magna. SAH+simvastatin group: Rats were subcutaneously injected daily with simvastatin (20 mg/kg, 0.1ml) for 7 days after the first puncture (day 0). Seven days later, neurological deficits were scored (5 to 27; 27=normal), then all rats were sacrificed immediately. Brain stem tissues were taken for paraffin section. Basilar artery(BA) was analyzed under light microscopy after hematoxylin-eosin staining. The internal diameter, D/T value(internal diameter/wall thickness) and degree of CVS were measured by image analysis system; Expression of eNOS protein and TNF-αprotein in BA wall were detected by immunohistochemistry.RESULTS: 1. Remarkable vasospasm of BA and neurological deficits, decreased expression of eNOS and increased expression of TNF-α(P＜0.05) were detected in SAH group, compared with the sham group. 2. In comparision with SAH group, cerebral vasospasm and neurological deficits in SAH+simvastatin group were significantly ameliorated (P＜0.05) with significantly higher expression of eNOS (P＜0.05) and lower expression of TNF-α(P＜0.05).CONCLUSIONS: Simvastatin treatment after SAH attenuated DCVS and neurological deficits in rat. The mechanism may be attributable partly to eNOS upregulation, and partly to TNF-αdownregulation.
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