HCN通道阻滞药CsCl对慢性脑缺血大鼠学习记忆的影响

Effects of HCN Channel Blocker CsCl on Learning and Memory in Rats with Chronic Cerebral Ischemia

目的:通过观察大鼠慢性脑缺血(CCH)后超极化激活环核苷酸门控阳离子(HCN)通道的表达变化以及给予HCN通道阻滞药氯化铯(CsCl)对CCH大鼠学习记忆的影响,为进一步深入揭示CCH引起认知损伤的机制及寻找新的干预靶点提供依据。方法:采用双侧颈总动脉结扎建立大鼠CCH模型。Western blot法检测CCH不同时间点大鼠海马CA1区HCN通道亚基HCN1和HCN2的表达变化。给予CsCl后应用水迷宫实验及新事物认知实验评价大鼠空间及非空间学习记忆的变化,记录场电位长时程增强(LTP)来评价大鼠海马CA1区突触可塑性的变化。结果:CCH能引起大鼠海马CA1区HCN2表达的持续增加。给予HCN通道阻滞药CsCl可减轻CCH所致的学习记忆损伤及LTP的抑制。结论:CsCl可改善CCH所致的认知损伤,其机制可能是通过作用于HCN2通道发挥的。

Objective:To observe the expression changes of hyperpolarization-activated cyclic nucleotide-gated(HCN)channels in hippocampal CA1 region of rats after chronic cerebral hypoperfusion(CCH),explore the effects of CsCl,a HCN channel blocker,on learning and memory of rats with CCH to provide approaches for further understanding the pathogenesis of cognitive impairment caused by CCH and search for a new intervention target.Methods:Two-vessel occlusion(2 V0)was adopted as a rat model of CCH.The expressions of HCN1 and HCN2 in hippocampal CA1 region of rats were tested by Western blot.Learning and memory were tested by Morris water maze experiment and novel object recognition test.Long-term potentiation(LTP)was tested to address the underlying synaptic mechanisms of the alteration of learning and memory.Results:CCH caused an increase of HCN2 expression in the hippocampus CA1 region of rats.CsCl could alleviate the learning and memory impairment,as well as inhibit LTP caused by CCH.Conclusion:CsCl can improve cognitive impairment caused by CCH,and its mechanism may target at HCN2 channel.