摘要
目的探讨外源性硫化氢(H2S)对APP/PS1转基因小鼠海马区tau蛋白磷酸化及对PI3K/Akt/GSK-3β信号通路的影响。方法将7月龄APP/PS1小鼠20只,随机分为模型组及硫氢化钠(NaHS)组,每组10只;另取同龄C57BL/6小鼠作为对照组,连续腹腔注射NaHS共6周,每天1次。HE染色检测脑组织病理学改变;TUNEL检测小鼠海马区神经细胞凋亡情况;Morris水迷宫检测各组小鼠的学习与记忆能力;免疫组化检测各组小鼠海马区tau、p-tau(Ser-202)、p-tau(Thr-231)及p-tau(Ser-396)蛋白表达情况;Western blot检测PI3K、Akt、GSK-3β、p-Akt及p-GSK-3β蛋白的表达。结果与模型组相比,NaHS组小鼠脑组织病理损伤明显改善;小鼠海马区神经细胞凋亡数量明显降低;小鼠逃避潜伏期明显缩短,单位时间内目标象限停留时间延长,穿台次数增加;p-tau(Ser-202)、p-tau(Thr-231)及p-tau(Ser-396)蛋白表达明显降低;同时,PI3K、p-Akt蛋白水平增加,而p-GSK-3β蛋白水平降低,差异有统计学意义(P<0.05)。结论 NaHS可减少神经细胞凋亡,抑制tau蛋白磷酸化,改善学习记忆能力,其机制可能与调控PI3K/Akt/GSK-3β信号通路活性有关。
Objective To investigate the effect of exogenous hydrogen sulfide(H2 S)on tau phosphorylation inhippocampus of APP/PS1 transgenic mice and its effect on PI3 K/Akt/GSK-3β signaling pathway.MethodsTwenty-eight-month-old APP/PS1 mice were randomly divided into model group and sodium hydrosulfide(Na HS)group,with 10 rats ineach group. C57 BL/6 mice of the same age were used as control group,and Na HS was injected intraperitoneally for 6 weeks,once a day. HE staining was used to detect the pathological changes of brain tissue;TUNEL was used to detect the apoptosisof hippocampus in mice;Morris water maze was used to detect the learning and memory ability of mice in each group;immunohistochemistry was used to detect tau and p-tau(Ser-202),p-tau(Thr-231)and p-tau(Ser-396)protein expressionin hippocampus of each group;Western blot detection of PI3 K,Akt,GSK-3β,p-Akt and p-GSK-3β protein expression.ResultsCompared with the model group,the pathological damage of brain tissue in the Na HS group was significantlyimproved;the number of neuronal apoptosis in the hippocampus of the mice was significantly reduced;The escape incubationperiod of mice was significantly shortened,the stay time in the target quadrant was prolonged,and the frequency of crossingthe platform was increased. The protein expressions of p-tau(Ser-202),p-tau(Thr-231)and p-tau(Ser-396)were signifi-cantly reduced. Meanwhile,the levels of PI3 K and p-Akt increased,while the levels of p-GSK-3β decreased,with statisti-cally significant differences(P<0.05).ConclusionNa HS reduces neuronal apoptosis,inhibits tau phosphorylation,andimproves learning and memory. The mechanism may be related to the regulation of PI3 K/Akt/GSK-3β signaling pathwayactivity.
作者
孙岩
SUN Yan(Department of Neurology,Tieling Central Hospital,Tieling,Liaoning Province 112000,China)
出处
《解剖学研究》
CAS
2019年第6期473-478,共6页
Anatomy Research
基金
辽宁省自然科学基金(20180551091)
