亚甲蓝影响异氟烷对老年阿茨海默病小鼠神经毒性的研究

Effect of methylene blue on Iso-induced neurotoxicity in geriatric mice with AD

目的探究亚甲蓝(methylene blue,MB)在老年阿茨海默病(Alzheimer’s disease,AD)小鼠模型中,对异氟烷(isoflurane,Iso)神经毒性的影响。方法12月龄野生型鼠(WT鼠)和AD转基因鼠(APP鼠)共分为4组。WTMB组和APPMB组:经尾静脉注入2 mg/kg亚甲蓝15 min后,吸入100%氧气(1 L/min);APP_(MB+Iso)组:注入2 mg/kg亚甲蓝后吸入1 U最低肺泡浓度(minimum alveolar concentration,MAC)异氟烷,氧流量为1 L/min;APP_(Iso)组:注射同体积生理盐水后吸入1 U MAC异氟烷。吸入氧气或异氟烷都为4 h。APP_(MB+Iso)组和APP_(Iso)组的1 MAC异氟烷经预实验测为1.4%。行Morris水迷宫检测学习与记忆,蛋白印迹实验检测Aβ_(1~42)和p-Tau水平。结果4组间潜伏时间有统计学差异(P<0.05),WTMB组学习能力最佳,APP_(Iso)组学习能力最差;WTMB组记忆能力最好,穿台次数明显多于其余3组(P<0.05),APP_(Iso)组记忆能力最差,穿台次数明显少于其余组(P<0.05)。4组间第1、3 dAβ_(1~42)和p-Tau水平有明显差异(P<0.05),WTMB组最低,APP_(Iso)组最高。结论注射2 mg/kg亚甲蓝能减轻异氟烷对老年AD小鼠神经毒性。

Objective To explore the effect of methylene blue(MB)on isoflurane(Iso)-induced neurotoxicity in geriatric mice with Alzheimer’s disease(AD).Methods The 12-month-old wild-type(WT)mice and transgenic mice with AD(APP mice)were divided into 4 groups.The mice in WTMB group and APPMB group were injected with 2 mg/kg MB through tail vein,and then inhaled100%oxygen(1 L/min)15 min later.And the mice in APP_(MB+Iso)group were injected with 2 mg/kg MB,and then inhaled 1 minimum alveolar concentration(MAC)of isoflurane,with 1 L/min oxygen.The mice in APP_(Iso)group were injected with the same volume of saline,and then inhaled 1 MAC of isoflurane.Inhalation of oxygen or isoflurane lasted for four hours.The 1 MAC of isoflurane in APP_(MB+Iso)group and APP_(Iso)group was 1.4%measured through preliminary experiment.The learning and memory behaviors were measured using the Morris water maze test.The expression levels of Aβ_(1~42)and p-Tau were analyzed with Western blotting.Results There were statistically significant differences in the latency times among the four groups(P<0.05).The mice had the best learning ability in WTMB group,while those had the worst learning ability in APP_(Iso)group.The numbers of crossing original platform in WTMB group with the best memory ability were significantly more than the other three groups(P<0.05),and those in APP_(Iso)group with the worst memory ability were significantly less than the other three groups(P<0.05).There were significant differences in levels of Aβ_(1~42)and p-Tau at day 1 and day 3 among the four groups(P<0.05),with the lowest in WTMB group,the highest in APP_(Iso)group.Conclusion The injection of 2 mg/kg MB could reduce the isoflurane-induced neurotoxicity in geriatric mice with Alzheimer’s disease.