X染色体上脆性X智力低下基因1敲除模型小鼠针刺长强穴学习记忆及海马CA1区γ-氨基丁酸A型受体α1亚基表达的影响

Effects of acupuncturing Changqiang acupoint on the learning and memory function and gamma-aminobutyric acid type A receptor alpha1 subunit expression in the hippocampal CA1 region of the fragile X mental retardation 1 located on X chromosome knockout mice

背景:X染色体上脆性X智力低下基因1敲除小鼠海马区γ-氨基丁酸A型受体α1亚基表达低于野生型小鼠。目的:观察针刺长强穴对X染色体上脆性X智力低下基因1敲除小鼠学习记忆及海马CA1区γ-氨基丁酸A型受体α1亚基表达的影响。方法:采用X染色体上脆性X智力低下基因1敲除纯合子小鼠雌雄各5只,一雌一雄合笼饲养。所繁殖幼鼠经基因型鉴定为X染色体上脆性X智力低下基因1敲除纯合子小鼠者,随机分为模型组、长强组、非穴组,各10只,另取野生型小鼠10只作为空白组。长强组小鼠采用平补平泻,行提插手法针刺长强穴1 min,频率160-200次/min,1次/d,连续治疗10 d;非穴组刺激小鼠右肋弓最低点上1 cm处;模型组及空白组每日只进行模拟抓取。结果与结论:与空白组相比,模型组小鼠水迷宫逃避潜伏期明显延长(P<0.05);而与模型组相比,长强组小鼠水迷宫逃避潜伏期明显缩短(P<0.05),海马CA1区γ-氨基丁酸A型受体α1亚基表达率增加(P<0.05);而非穴组小鼠水迷宫逃避潜伏期及海马CA1区γ-氨基丁酸A型受体α1亚基表达率与模型组接近(P>0.05)。且针刺X染色体上脆性X智力低下基因1敲除小鼠长强穴后其海马CA1区γ-氨基丁酸A型受体α1亚基阳性细胞率与逃避潜伏期呈负相关(r=-0.554,P=0.001)。提示针刺长强穴可改善X染色体上脆性X智力低下基因1敲除小鼠的学习记忆能力,上调γ-氨基丁酸A型受体α1亚基在海马CA1区的表达。

BACKGROUND： γ-Aminobutyric acid type A receptor α1 subunit expression was lower in the hippocampus of mice of fragile X mental retardation 1（FMR1） gene located on the X chromosome knockout than in wild-type mice. OBJECTIVE： To study the effect of acupuncturing Changqiang（DU1） point on the learning and memory function and γ-aminobutyric acid type A receptor α1 subunit expression in the hippocampal CA1 region of the FMR1 located on X chromosome knockout mice.METHODS： There were five male and five female homozygous mice of FMR1 located on X chromosome knockout.One female and one male were housed in a cage. Their offspring that was identified as homozygous mice of FMR1 located on X chromosome knockout were randomly divided into model group, Changqiang group, and non-acupuncture group（n=10）. An additional 10 wild-type mice were considered as blank group. Mice in the Changqiang group received acupuncture at Changqiang acupoint for 1 minute by mild reinforcing and attenuating method, and lifting and inserting method, at the frequency of 160-200 times/minute, once a day, for 10 consecutive days. Mice in the non-acupuncture group were acupunctured at 1 cm above the lowest point of mouse right costal arch. Mice in the model and blank groups only received analog crawl. RESULTS AND CONCLUSION： Compared with the blank group, the escape latency in the water maze was significantly prolonged in the model group（P 〈0.05）. Compared with the model group, the escape latency in the water maze was significantly shorter in the Changqiang group（P 〈0.05）, and the γ-aminobutyric acid type A receptor α1 subunit expression in the hippocampal CA1 region was increased（P 〈0.05）. The escape latency in the water maze and γ-aminobutyric acid type A receptor α1 subunit expression in the hippocampal CA1 region were similar between the non-acupuncture and model groups（P 〉0.05）. Moreover, γ-aminobutyric acid type A receptor α1 subunit expression in the hippocampal CA1 region was negatively associated with the escape latency after acupuncturing the Changqiang acupoint（r=-0.554, P=0.001）. Data suggested that acupuncture at Changqiang acupoint improved the learning and memory capabilities of mice with the FMR1 located on X chromosome knockout, and up-regulated γ-aminobutyric acid type A receptor α1 subunit expression in the hippocampal CA1 region.