Zhu Jing-Jing, Xiang Chen, Wu Shu-Hui, Jiang Ting-Ting, Zhou Jie-Yu, Li Xin-Qian, Wu Xue-Jun, Yan Yong
Department of Otolaryngology, Baoshan Branch, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine Shanghai 201900, People's Republic of China.
Department of Thyroid Surgery, Baoshan Branch, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine Shanghai 201900, People's Republic of China.
Am J Transl Res. 2019 Jul 15;11(7):4203-4213. eCollection 2019.
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.
本研究旨在探讨丹参酮IIA（Tan）治疗缺血性眩晕作用的分子机制。将雄性Sprague-Dawley（SD）大鼠分为假手术组、模型组、模型+PBS组、模型+Tan（10mg/kg）组、模型+Tan（20mg/kg）组、模型+Tan（40mg/kg）组和模型+Tan（80mg/kg）组。观察不同组大鼠的逃避潜伏期，同时通过苏木精-伊红（H&E）染色、蛋白质免疫印迹法（Western Blot）和免疫组化（IHC）检测体内外一氧化氮（NO）/环磷酸鸟苷（cGMP）的生成及大电导钙激活钾通道（BKCa）的表达。缺血性眩晕大鼠的逃避潜伏期延长，而Tan（40mg/kg及以上）治疗可缩短缺血性眩晕大鼠的逃避潜伏期。此外，40mg/kg或80mg/kg Tan治疗后，模型组中降低的NO/cGMP生成及BKCa蛋白表达有一定程度的增加。对不同大鼠组收集的前庭内侧核（MVN）神经元细胞进行H&E染色也证实了Tan对受损MVN神经元细胞修复的积极作用。此外，上述结果在体外也得到了验证，用5μg/ml和10μg/ml Tan处理的细胞增加了NO/cGMP生成水平及BKCa蛋白表达。在一定剂量下，Tan可增加NO和cGMP的生成以及BKCa的表达，进而有助于缺血性眩晕的治疗。
