Guo Xin, Chen Zheng-Hua, Wang Hui-Ling, Liu Zhong-Chun, Wang Xiao-Ping, Zhou Ben-Hong, Yang Can, Zhang Xue-Ping, Xiao Ling, Shu Chang, Chen Jian-Xin, Wang Gao-Hua
Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Mol Med Rep. 2015 Apr;11(4):2927-34. doi: 10.3892/mmr.2014.3086. Epub 2014 Dec 12.
Warm‑supplementing kidney yang (WSKY) is an herbal prescription that has been used in Traditional Chinese Medicine for the treatment of psychiatric conditions. A previous study by our group found that WSKY significantly improved cognitive function of schizophrenia patients. In the present study, the effects of WSKY on cognitive function and their underlying mechanisms were investigated. WSKY was administered to an MK‑801‑induced rat model of chronic schizophrenia for 14 days. Memory performance was assessed using the Morris water maze (MWM) test. The expression of brain‑derived neurotrophic factor (BDNF), activation of cAMP response element binding protein (pCREB/CREB) and activation of extracellular signal‑regulated kinase (pERK/ERK) in the hippocampus was detected using western blot analysis. In the acquisition phase of the MWM test, the escape latency was significantly increased in the MK‑801‑treated group compared with the normal control group (P<0.01). Treatment with WSKY for 14 days at doses of 100 or 250 mg/kg rescued this cognitive impairment (P<0.05). In the probe test, 250 mg/kg WSKY treatment increased the time spent in the target quadrant (P<0.05) and number of platform crossings (P<0.01). Western blot analysis demonstrated that the levels of BDNF expression in the hippocampus of rats without behavioral tests were elevated following 14 days of WSKY treatment, and the effect of WSKY treatment on hippocampal BDNF expression was presented in an inverted U‑shaped dose‑response pattern. The pERK1/2 in the hippocampus was significantly enhanced following 100 mg/kg (P<0.01) and 250 mg/kg (P<0.01) WSKY treatment, while only 250 mg/kg WSKY increased the phosphorylation of CREB (P<0.01). The results of the present study indicated that WSKY enhances cognitive performance via the upregulation of BDNF/ERK/CREB signaling, and that WSKY has potential therapeutic implications for cognitive impairment of schizophrenia.
温补肾阳是一种在中医中用于治疗精神疾病的草药方剂。我们团队之前的一项研究发现，温补肾阳能显著改善精神分裂症患者的认知功能。在本研究中，对温补肾阳改善认知功能的作用及其潜在机制进行了研究。将温补肾阳给予MK-801诱导的慢性精神分裂症大鼠模型，持续给药14天。使用莫里斯水迷宫（MWM）试验评估记忆表现。采用蛋白质免疫印迹分析检测海马中脑源性神经营养因子（BDNF）的表达、环磷酸腺苷反应元件结合蛋白的激活（pCREB/CREB）以及细胞外信号调节激酶的激活（pERK/ERK）。在MWM试验的获取阶段，与正常对照组相比，MK-801处理组的逃避潜伏期显著延长（P<0.01）。以100或250mg/kg的剂量给予温补肾阳治疗14天可挽救这种认知障碍（P<0.05）。在探针试验中，250mg/kg温补肾阳治疗增加了在目标象限的停留时间（P<0.05）和穿越平台的次数（P<0.01）。蛋白质免疫印迹分析表明，在未进行行为测试的大鼠海马中，温补肾阳治疗14天后BDNF表达水平升高，且温补肾阳治疗对海马BDNF表达的影响呈倒U形剂量反应模式。100mg/kg（P<0.01）和250mg/kg（P<0.01）温补肾阳治疗后，海马中的pERK1/2显著增强，而只有250mg/kg温补肾阳增加了CREB的磷酸化（P<0.01）。本研究结果表明，温补肾阳通过上调BDNF/ERK/CREB信号通路增强认知表现，且温补肾阳对精神分裂症的认知障碍具有潜在治疗意义。
