天香胶囊对晕动病模型大鼠前庭核NMDAR1信号通路的影响*

目的:观察天香胶囊对晕动病模型大鼠前庭核NMDAR1(N-甲基-D-天冬氨酸受体1,N-methyl-D-aspartate acid receptor 1)、P-CaMKⅡ (磷酸化钙调蛋白激酶Ⅱ-亚基,the phosphorylation of calmodulin protein kinase Ⅱ alpha subunit)、P-CREB(磷酸化cAMP反应元件结合蛋白,the phosphorylation of cAMP response element binding protein)表达的影响,探讨天香胶囊调节晕动病模型大鼠前庭核兴奋性的内在分子机制。方法:将36只雄性SD大鼠随机分为正常对照组、模型组、阳性药对照组(东莨菪碱)、天香胶囊低、中、高剂量组。灌胃预给药3天后,采用双轴旋转刺激法复制大鼠晕动病模型,通过Western blotting法检测各组大鼠前庭核NMDAR1、P-CaMKⅡ/CaMKⅡ、P-CREB/CREB的表达情况。结果:与正常组大鼠相比,模型组大鼠前庭核NMDAR1、P-CaMKⅡ、P-CREB蛋白表达水平显著增加;与模型组相比,中、高剂量天香胶囊可显著下调晕动病模型大鼠前庭核组织NMDAR1、P-CaMKⅡ、P-CREB蛋白表达。结论:天香胶囊可抑制晕动病模型大鼠前庭核NMDAR1信号通路的活化,这可能是其在治疗晕动病中降低前庭核兴奋性的内在分子机制之一。

Effects of Tianxiang Capsule on the NMDAR1 Signaling Pathway in the Vestibule Nucleus of Rats with Motion Sickness*

ABSTRACT Objective: To detect the effects of Tianxiang capsule on NMDAR1(N-methyl-D-aspartate acid receptor 1), P-CaMKII (the phosphorylation of calmodulin protein kinase II alpha subunit) and P-CREB(the phosphorylation of cAMP response element binding protein) expression and investigate the molecular mechanism of Tianxiang capsule on regulating the excitability of vestibular nucleus in rats with motion sickness. Methods: 36 cases of male SD rats were randomly divided into six groups, including normal group, model group, scopolamine group, low-dose, mid-dose and high-dose Tianxiang capsule groups. The drugs were intragastrically administrated for 3 days, and then the motion sickness model was induced by biaxial rotation stimulus. The expression of NMDAR1, P-CaMKII /CaMKII and P-CREB/CREB in the vestibule nucleus of rats in each group was detected by Western Blotting. Results: Compared with the normal group, the expression of NMDAR1 and phosphorylation of CaMKII and CREB were significantly up-regulated in the model group. Compared with the model group, NMDAR1 signaling pathway was significantly inhibited in mid-dose and high-dose Tianxiang capsule groups. Conclusion: Tianxiang capsule can inhibit NMDAR1 signaling pathway in the vestibule nucleus of rats with motion sickness. This may be one of the pharmacological mechanisms of Tianxiang capsule for inhibiting the excitability of vestibular nucleus in the treatment of motion sickness.