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

SUN Juan; ZHANG Yan; CHEN Chun-Hua

doi:10.16098/j.issn.0529-1356.2021.06.003

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

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

SUN Juan¹ ZHAO Xiu-li¹ZENG Guo-xi¹ ZHANG Yan^2* CHEN Chun-hua^2*

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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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SUN Juan ZHAO Xiu-li ZENG Guo-xi ZHANG Yan CHEN Chun-hua. Salvinorin A alleviating cerebral vasospasm after subarachnoid hemorrhage through phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase pathway[J]. Acta Anatomica Sinica. 2021, 52(6): 855-862 https://doi.org/10.16098/j.issn.0529-1356.2021.06.003

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