Identification of molecular mechanism underlying therapeutic effect of tanshinone IIA in the treatment of hypoxic vestibular vertigo via the NO/cGMP/BKCa signaling pathway.

This study aimed to investigate the molecular mechanisms underlying the effect of Tashinone IIA (Tan) on the treatment of ischemic vertigo. Sprague-Dawley (SD) male rats were divided into a SHAM group, a MODEL group, a MODEL+PBS group, a MODEL+Tan (10 mg/kg) group, a MODEL+Tan (20 mg/kg) group, a MODEL+Tan (40 mg/kg) group and a MODEL+Tan (80 mg/kg) group. The escape latency was observed among different groups of rats, while the production of NO/cGMP and the expression of BKCa were measured in vivo and in vitro by H&E staining, Western Blot and IHC assays. While the rats with ischemic vertigo showed prolonged escape latency, the treatment by Tan (40 mg/kg and up) shortened the escape latency in rats with ischemic vertigo. Moreover, the reduced production of NO/cGMP and expression of BKCa protein in the MODEL group were increased by a certain extent upon the treatment of 40 mg/kg or 80 mg/kg Tan. H&E staining of MVN neuron cells collected from different rat groups also validated the positive effects of Tan on the repair of damaged MVN neuron cells. Moreover, the above results were also validated in vitro, as the cells treated with 5 ug/ml and 10 ug/ml Tan increased the levels of NO/cGMP production and BKCa protein expression. At a certain dose, Tan could increase the production of NO and cGMP as well as the expression of BKCa, which would subsequently aid the treatment of ischemic vertigo.