Anti-apoptotic effect of Astragaloside IV on delayed cerebral vasospasm following subarachnoid hemorrhage in rats

Abstract

Objective Investigate the effect of Astragaloside Ⅳ (AS-Ⅳ) on delayed cerebral vasospasm (DCVS) following subarachnoid hemorrhage. Methods The male SD rats were divided into Sham group (A), SAH+ AS-Ⅳ group (B), SAH model group (C) and SAH+ vehicle group (D). The model of DCVS following subarachnoid hemorrhage was made by the double injection method of occipital cistern. During the 5 days after model success, rats in the B group were treated with daily AS-Ⅳ (20 mg/kg) which was dissolved in 5% alcohol; rats in the D group were injected with identical volume of physiological saline containing 5% alcohol; rats in the SAH group and the Sham group were inject with identical volume of physiological saline. Morphological changes of basilar artery was observed by hematoxylin and eosin (HE) staining. The apoptosis of basilar artery endothelial cells and vascular smooth muscle cells was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. The cleaved cysteinyl aspartate-specific protease (Caspase)-3 expression in basilar artery was detected by immunohistochemical staining. The expression of B cell lymphoma/leukemia-2 (bcl-2), bcl-2 associated X protein (bax) and cleaved Caspase-3 was detected by Western blotting. Results Compared with Sham group, the basilar artery wall became thicker and lumen cross-sectional area became smaller. The expression of bax and cleaved Caspase-3 (P<0.05) was decreased in basilar artery (P<0.05). Compared with SAH+ vehicle group and SAH group, the expression of cleaved Caspase-3 in SAH+ AS-Ⅳ group increased (P<0.05) and the expression of bax and cleaved Caspase-3 decreased after AS-Ⅳ intervention (Cleaved Caspase-3: 0.030 8±0.003 2 vs. 0.070 4±0.006 0, 0.069 0±0.005 7, P<0.05). Conclusion AS-Ⅳ can relieve delayed cerebral vasospasm and its mechanism may be related to the fact that AS-Ⅳ can interfere with the apoptosis signaling pathway mediated by bcl-2, bax and Caspase-3. Key words: Astragaloside Ⅳ; Subarachnoid hemorrhage; Delayed cerebral vasospasm; Apoptosis