Song Xiaomei, Wang Wei, Kang Yaguo, Zhang Xin, Jiang Yi, Yue Zhenggang, Tang Zhishu
Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Shaanxi Rheumatism and Tumor Center of TCM Engineering Technology Research, School of Pharmacy, Shaanxi University of Chinese Medicine Xianyang 712046, China.
Int J Clin Exp Med. 2015 Jun 15;8(6):9013-21. eCollection 2015.
Previous studies have suggested that diabetes significantly impairs the cognitive function. Tangzhining (TZN), as a kind of Traditional Chinese Medicine (TCM), has been widely used to treat diabetes in China. However, the effect of TZN on treatment of diabetes-induced learning and memory deficits has not been well documented. The present study was to investigate the effect of TZN on diabetes-induced learning and memory deficits and delineate the underlying molecular mechanism. Diabetic rats were randomly grouped and treated with various doses of TZN (0.47, 0.94 and 1.4 g/kg) by intraperitoneal injection. Using the Morris water maze, TZN treatment (0.94 g/kg and 1.4 g/kg) reduced markedly the escape latency and path length of diabetic rats. The morphological changes of pyramidal cells in hippocampus of diabetic rats were apparently reversed and improved by TZN treatment, in comparison with that in diabetic rats without TZN treatment. Moreover, the results of Western blot analysis showed that TZN treatment significantly increased the protein expression of glutamic acid decarboxylase (GAD) and excitatory amino acid carrier 1 (EAAC1) in hippocampus of diabetic rats. Furthermore, TZN treatment increased the protein expression of N-methyl-D-aspartic acid (NMDA) receptor subunits including NR1 and NR2B. Taken together, our data suggest that TZN sustains the balance between glutamate (Glu) and GABA by regulating GAD and EAAC1, and maintains the NMDA receptors activity for learning and memory function through regulating the subunits NR1 and NR2B.
先前的研究表明，糖尿病会显著损害认知功能。糖脂宁（TZN）作为一种中药，在中国已被广泛用于治疗糖尿病。然而，TZN对糖尿病所致学习和记忆缺陷的治疗效果尚未得到充分记载。本研究旨在探讨TZN对糖尿病所致学习和记忆缺陷的影响，并阐明其潜在的分子机制。将糖尿病大鼠随机分组，通过腹腔注射给予不同剂量的TZN（0.47、0.94和1.4 g/kg）。使用Morris水迷宫实验，TZN治疗（0.94 g/kg和1.4 g/kg）显著缩短了糖尿病大鼠的逃避潜伏期和路径长度。与未接受TZN治疗的糖尿病大鼠相比，TZN治疗明显逆转并改善了糖尿病大鼠海马中锥体细胞的形态变化。此外，蛋白质印迹分析结果显示，TZN治疗显著增加了糖尿病大鼠海马中谷氨酸脱羧酶（GAD）和兴奋性氨基酸转运体1（EAAC1）的蛋白表达。此外，TZN治疗增加了包括NR1和NR2B在内的N-甲基-D-天冬氨酸（NMDA）受体亚基的蛋白表达。综上所述，我们的数据表明，TZN通过调节GAD和EAAC1维持谷氨酸（Glu）和γ-氨基丁酸（GABA）之间的平衡，并通过调节亚基NR1和NR2B维持NMDA受体活性以发挥学习和记忆功能。
