Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (6): 855-862.doi: 10.16098/j.issn.0529-1356.2021.06.003

• Neurobiology • Previous Articles     Next Articles

Salvinorin A alleviating cerebral vasospasm after subarachnoid hemorrhage through phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase pathway

SUN Juan1  ZHAO Xiu-liZENG Guo-xi ZHANG Yan2* CHEN Chun-hua2*   

  1. 1. Department of Neurology, Qinghai University Affiliated Hospital, Xining 810001,China; 2. Department of Human Anatomy and Histology Embryology, School of Basic Medical Sciences,  Peking University Health Science Center, Beijing  100083,China
  • Received:2020-06-24 Revised:2020-07-14 Online:2021-12-06 Published:2021-12-06
  • Contact: ZHANG Yan;CHEN Chun-hua E-mail:cch@bjmu.edu.cn

Abstract:

Objective  To investigate the effect of salvinorin A (SA) on alleviating cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH).    Methods  The SAH models were established by endovascular perforation method . Adult male SD rats (n=97) were randomly divided into the sham group (sham), SAH model group (SAH), control group (SAH+DMSO) and drug administration group (SAH+SA). SA and DMSO were diluted with saline, and injected intraperitoneally at hour 24, hour 48 and hour 72 after SAH. At hour 72 after SAH, the neurological score was evaluated. The diameter and wall thickness of the internal carotid artery were observed through HE staining. Endothelin 1 (ET-1) ELISA kit and nitric oxide (NO) kit were used to observe the ET-1 concentration and NO content on the blood vessels of Willis circle. The expression of phosphorglated PI3K(p-PI3K), PI3K, phosphorylated Akt(p-Akt), Akt and endothelial nitric oxide synthase (eNOS) proteins were detected by  Western blotting and the location of eNOS protein was observed by immunofluorescent staining.   Results  At hour 72 after SAH, SA could increase the neurological score, increase the vessel diameter and reduce the wall  thickness of internal carotid artery. SA could reduce the ET-1 concentration and increase NO content in the blood vessels of Willis circle at hour 72 after SAH. SA could increase the ratio of p-PI3K/PI3K, p-Akt/Akt and the expression of eNOS proteins, which could be inhibited by PI3K inhibitor wortmannin and eNOS inhibitor  L-NAME. eNOS expressed in vascular endothelial cells was detected by the immunofluorescence staining.    Conclusion  SA can alleviate CVS after SAH through PI3K/Akt/eNOS pathway. 

Key words: Subarachnoid hemorrhage, Cerebral vasospasm, Salvinorin A, Western blotting, Immunofluorescence, Rat

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