Background:
The aim of the present study was to investigate the protective effects of Tanshinone IIA
(Tan IIA) on hypoxia-induced injury in the medial vestibular nucleus (MVN) cells.
Methods:
An in vitro hypoxia model was established using MVN cells exposed to hypoxia. The hypoxia-induced
cell damage was confirmed by assessing cell viability, apoptosis and expression of apoptosis-associated proteins.
Oxidative stress and related indicators were also measured following hypoxia modeling and Tan IIA treatment,
and the genes potentially involved in the response were predicted using multiple GEO datasets.
Results:
The results of the present study showed that Tan IIA significantly increased cell viability, decreased cell
apoptosis and decreased the ratio of Bax/Bcl-2 in hypoxia treated cells. In addition, hypoxia treatment increased
oxidative stress in MVN cells, and treatment with Tan IIA reduced the oxidative stress. The expression of SPhase
Kinase Associated Protein 2 (SKP2) was upregulated in hypoxia treated cells, and Tan IIA treatment reduced
the expression of SKP2. Mechanistically, SKP2 interacted with large-conductance Ca2+-activated K+ channels
(BKCa), regulating its expression, and BKCa knockdown alleviated the protective effects of Tan IIA on
hypoxia induced cell apoptosis.
Conclusion:
The results of the present study suggested that Tan IIA had a protective effect on hypoxia-induced
cell damage through its anti-apoptotic and anti-oxidative activity via an SKP2/BKCa axis. These findings suggest
that Tan IIA may be a potential therapeutic for the treatment of hypoxia-induced vertigo.
Primary cholinergic input to medial vestibular nucleus neuron responding to tilt stimulation
