Abstract:
OBJECTIVE:In the present study, we used a two-kidney-two-clip (2k2c) stroke-prone renovascular hypertension rat model (RHRSP) to investigate the protective effects of ligustrazine (TMP) on cerebral arteries and to examine PI3K/Akt pathway behavior under this protection. METHODS:The cerebral artery remodeling was induced by 2k2c-induced renovascular hypertension. Brain basilar artery tissues were isolated and their histological changes were detected through H&E and EVG staining, α-SMA IHC staining, and transmission electron microscopy at four, eight, and twelve weeks after 2k2c surgery, both with and without TMP treatment. Meanwhile, the ET-1, Ang II, and NO levels in basilar arteries and plasma were determined. Furthermore, the PTEN expression and the activation of PI3K/Akt in basilar artery tissues were detected through IHC and Western Blot. In addition, the primary basilar artery smooth muscle cells (BASMCs) were cultured and TMP protection of BASMCs stimulated with ET-1/Ang II in the presence or absence of insulin-like growth factor 1 (IGF-1) was determined. RESULTS:TMP attenuated basilar artery remodeling, decreased ET-1 and Ang II levels and increased NO level in basilar arteries and plasma of RHRSP rats. Moreover, TMP reduced BASMCs proliferation upon ET-1/Ang II stimulation. We also found that TMP could effectively suppress the activation of PI3K/Akt in 2k2c-RHRSP rat basilar artery and ET-1/Ang II stimulated BASMCs. Most importantly, IGF-1, as an activator of PI3K/Akt, could damage the protective effect of TMP. CONCLUSIONS:TMP exerts its protective effects and prevents basilar artery remodeling in RHRSP rats at least partly through the inhibition of PI3K/Akt pathway.
journal_name
Microvasc Resjournal_title
Microvascular researchauthors
Zhang B,Zhang Y,Deng F,Fang Sdoi
10.1016/j.mvr.2019.103938subject
Has Abstractpub_date
2020-03-01 00:00:00pages
103938eissn
0026-2862issn
1095-9319pii
S0026-2862(19)30103-7journal_volume
128pub_type
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