Effect of simvastatin on proliferation of vascular smooth muscle cells during delayed cerebral vasospasm after subarachnoid hemorrhage
Recently, many studies reported that it may be related with the proliferation of vascular smooth muscle cells (VSMCs) (5, 9) . Platelet-derived growth factor-β (PDGF-β) is a polypeptide which could stimulate vascular smooth muscle cell and matrix proliferation (14). Proliferating cell nuclear antigen (PCNA) is a marker of deoxyribonucleic acid (DNA) synthesis, and it can be considered as an index in evaluating cell proliferation (20). α-smooth muscle actin (α-SMA) is an important functional
... tant functional protein in VSMCs, and the change of its expression could █ INTRODUCTION Stroke is one of the leading causes of death and the main reason for long-term disability. Five percent patients with stroke are caused by subarachnoid hemorrhage (SAH) (13). Delayed cerebral vasospasm (dCVS) is a common and dangerous complication of SAH. It usually occurs within 4-15 days after SAH and results in serious and irreversible delayed cerebral injury (DCI). dCVS is the main cause of morbidity and mortality after SAH (1). But the pathogenesis of dCVS is still unclear. AIM: To explore the effect of simvastatin on proliferation of vascular smooth muscle cells (VSMCs) during delayed cerebral vasospasm (dCVS) after subarachnoid hemorrhage (SAH). MATERIAL and METHODS: Thirty-six male New Zealand White rabbits were randomly divided into three groups: 1) Control group (n=12): given conventional breeding and normal sodium (0.9%) was injected twice into the cisterna magna. 2) SAH group (n=12): given conventional breeding and a SAH model was established. 3) Simvastatin + SAH group (n=12): given conventional breeding and simvastatin for one week, and then a SAH model was established. The first cerebral angiography was conducted before the first injection of sodium or autologous blood into the cisterna magna. The second angiography was done three days after the second injection. The ultrastructural pathology of the basilar artery was compared in three groups. The expression of platelet-derived growth factor-β (PDGF-β), proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in VSMCs was analysed by RT-PCR. RESULTS: Angiography examinations showed that the basilar artery was obviously contracted in the SAH group and dCVS was confirmed existence after blood injection into the cisterna magna twice. The thickness of VSMCs in the SAH group increased and the expression of PDGF-β, PCNA, and α-SMA in SAH group were all increased compared to the control group (p<0.05), and decreased while prophylactic giving simvastatin (p<0.05). CONCLUSION: Simvastatin may relieve dCVS after SAH by inhibiting the proliferation of VSMCs.