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目的探讨盐酸川芎嗪对低压低氧大鼠学习记忆功能的影响及其作用机制。方法将120只SD大鼠随机分为2组,低氧对照组(5 500 m)、低氧药物组(5 500 m),按时间段不同又分为1 d、3 d、7 d、15 d、30 d组,每组12只;对照组和药物组在模拟海拔5500 m的低压氧仓造模,对照组腹腔注射生理盐水,药物组用同样的方法注射盐酸川芎嗪进行干预。用Morris水迷宫实验检测大鼠行为学变化;Western blot检测大鼠海马GABAAα1R、GABAB1R、FOXP2表达情况。结果(1)通过计算对照组和药物组定位航行实验中的总路程和穿越平台次数可以得出,两组1 d结果差异无统计学意义(P>0.05),从3 d组开始,药物组总路程较对照组逐渐缩短(P<0.01),而穿越中心平台次数较对照组逐渐增多(P<0.01);(2)Western blot检测海马GABAAα1R受体,不同时间段对照组与药物组海马中该受体表达差异无统计学意义(P>0.05);GABAB1R受体和FOXP2蛋白,1 d对照组药物组表达没有差异,从3 d组开始,对照组该受体和蛋白表达量均低于药物组(P<0.05);(3)对照组海马中GABAB1R与水迷宫总路程呈负相关(r=-0.738,P<0.05);对照组海马中FOXP2蛋白与水迷宫总路程呈负相关(r=-0.693,P<0.05);对照组海马中GABAB1R、FOXP2蛋白表达呈正相关(r=0.834,P<0.05)。结论盐酸川芎嗪对低压低氧大脑学习记忆能力起到一定的保护作用,其机制可能与增加大鼠脑内递质GABAB1R和蛋白FOXP2表达量有关。
Objective To investigate the effect of ligustrazine hydrochloride on learning and memory in hypobaric hypoxia rats and its mechanism. Methods 120 Sprague-Dawley rats were randomly divided into 2 groups: hypoxia control group (5 500 m) and hypoxia drug group (5 500 m). The rats were divided into 1 d, 3 d, 7 d, 15 d d and 30 d groups, with 12 rats in each group. The control group and the drug group were established in a hypobaric oxygen chamber at an altitude of 5500 m. The control group was injected with saline intraperitoneally. The drug group was injected with ligustrazine hydrochloride by the same method. Morris water maze test was used to detect the behavioral changes in rats; Western blot was used to detect the expression of GABAAα1R, GABAB1R and FOXP2 in the hippocampus of rats. Results (1) By calculating the total distance of the control group and the drug group in positioning navigation experiment and the number of crossing the platform, there was no significant difference between the two groups on the first day (P> 0.05). From the 3 d group, (2) The level of GABAAα1R receptor in the hippocampus was detected by Western blot. The changes of the total distance between the control group and the hippocampus of the drug group were significantly lower than those of the control group (P <0.01) The expression of GABAB1R receptor was not significantly different from that of FOXP2 protein and control group for 1 day (P> 0.05). The expression of GABAB1R receptor and protein in control group was lower than that of control group (P <0.05). (3) The GABAB1R in the control group was negatively correlated with the total length of the water maze (r = -0.738, P <0.05). The FOXP2 protein in the control group was negatively correlated with the total length of the water maze r = -0.693, P <0.05). The protein expression of GABAB1R and FOXP2 in the control group was positively correlated (r = 0.834, P <0.05). CONCLUSION Tetramethylpyrazine hydrochloride may play a protective role in learning and memory ability of hypobaric hypoxia. The mechanism may be related to increasing the expression of GABAB1R and FOXP2 in rat brain.