Atorvastatin ameliorates early brain injury through inhibition of apoptosis and ER stress in a rat model of subarachnoid hemorrhage

作者：Qi, Wentao; Cao, Demao; Li, Yucheng; Peng, Aijun; Wang, Youwei; Gao, Kai; Tao, Cunshan; Wu, Yongkang^*

来源：Bioscience Reports, 2018, 38(3): BSR20171035.

DOI：10.1042/BSR20171035

• CEREBRAL VASOSPASM
• BCL-2 FAMILY
• CASPASE INHIBITORS
• SIMVASTATIN
• ISCHEMIA
• STATINS
• PRAVASTATIN
• MECHANISMS
• BIM

Aneurysmal subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease with very poor prognosis. The aim of the present study was to evaluate the protective effects of atorvastatin on early brain injury (EBI) after SAH using a perforation SAH model. Male Sprague-Dawley rats were randomly divided into four groups: the sham group, the SAH group (model group), SAH + 10 mg.kg(-1).day(-1) atorvastatin (low atorvastatin group), and SAH + 20 mg.kg(-1).day(-1) atorvastatin (high atorvastatin group). Atorvastatin was administered orally by gastric gavage for 15 days before operation. At 24 h after SAH, we evaluated the effects of atorvastatin on brain water content, apoptosis by TUNEL assay and scanning electron microscope (SEM), and the expression of apoptosis-related proteins by immunofluorescence and Western blotting analysis. Compared with the sham group, we observed increased brain water content, significant apoptosis, and elevated levels of apoptosis-related proteins including caspase-3, CCAAT enhancer-binding protein homologous protein (CHOP), the 78-kDa glucose-regulated protein (GRP78), and aquaporin-4 (AQP4) in the SAH group. Atorvastatin administration under all doses could significantly reduce brain water content, apoptosis, and the expression levels of caspase-3, CHOP, GRP78, and AQP4 at 24 h after SAH. Our data show that early treatment with atorvastatin effectively ameliorates EBI after SAH through anti-apoptotic effects and the effects might be associated inhibition of caspase-3 and endoplasmic reticulum (ER) stress related proteins CHOP and GRP78.

• 出版日期2018-5-15
• 单位扬州大学