青蒿素对老年小鼠学习记忆及炎性细胞因子和单胺类神经递质的影响

Effects of artemisinin on learning and memory, inflammatory cytokines and monoamine neurotransmitters in aged mice

目的探讨青蒿素对老年小鼠记忆能力的改善作用及对炎性细胞因子和单胺类神经递质的影响。方法30只22月龄老年小鼠随机分成老年小鼠模型对照组、青蒿素小剂量组（饲料中含青蒿素0．1％）和青蒿素大剂量组（饲料中含青蒿素0．3％），每组10只。另设10只2月龄小鼠作为青年小鼠模型对照组；给药组连续10周喂饲含青蒿素饲料，老年小鼠模型对照组和青年小鼠模型对照组喂饲标准饲料。采用Morris水迷宫实验检测小鼠的记忆能力、Elisa法检测小鼠血清炎性因子（IL-6和TNF-α）水平、HPLC法分析小鼠脑中神经递质（多巴胺、去甲肾上腺素和5-羟色胺）的含量。结果（1）水迷宫隐形平台实验中，老年小鼠模型对照组与青年小鼠模型对照组相比在水中滞留时间明显延长（P〈0．05）；青蒿素小剂量组和青蒿素大剂量组与老年小鼠模型对照组相比在水中滞留时间明显缩短（P〈0．05）。在反向隐性平台实验的第9天，青蒿素小剂量组[（50．1±19．9）S]及青蒿素大剂量组[（43．2±17．6）s]在水中滞留时间与老年对照组[（66．1±29．1）S]相比显著缩短（P〈0．05）。（2）血清炎性因子测定实验中，青蒿素小剂量组[IL-6：（28．4±4．3）pg／ml，TNF—α：（51．8±8．2）pg／ml]和青蒿素大剂量组[IL-6：（17．6±2．3）pg／ml，TNF-α：（38．6±12．5）pg／ml]IL-6与TNF—α水平与老年小鼠模型对照组[IL-6：（36．12±7．98）pg／ml），TNF-α：（67．32±10．27）pg／ml）]相比显著降低（P〈0．05）。（3）脑组织神经递质含量测定中，青蒿素小剂量组DA[（19．96±3．89）mmol／ml]、5-HT[（5．73±0．93）mmol／ml]含量高于老年小鼠模型对照组，青蒿素大剂量组DA[（26．13±5．66）mmol／ml]、NE[（16．31±2．69）mmol／ml]、5-HT[（8．03±1．93）mmol／ml]含量高于老年小鼠模型对照组[DA（13．96±3．89）mmol／ml，NE（8．73±2．16）mmol／ml，5-HT（3．82±1．09）mmol／ml]，均差异有统计学意义（均P〈0．05）。结论青蒿素对老年小鼠学习记忆能力降低具有改善作用，其机制可能与其抑制老年小鼠炎症发生和促进老年小鼠脑内神经递质水平相关。

Objective To investigate whether the arterrnisinin has beneficial efficacy to improve the learning and memory in aged mice, as well as the possible mechanisms regarding the inflammatory cytokines and monoamlne neurotransmitters. Methods 30 aged mice（22 month old） were randomly divided into the aged mouse model control group （n= 10）, the artemisinin low dose group （artemisinin 0. 1% in feed, n= 10 ） and the artemisinin high dose group （artemisinin 0.3% in feed, n= 10）. Another 10 mice （2 month old） served as young mouse model eontrol group. The artemisinin low dose group and the artemisinin high dose group fed artemisinin feed for 10 weeks. The aged mouse model control group and the young mouse model control group were fed standard feed.Morris water maze test was performed to assess learning and memory capacities for evaluation of the cognitive degree. Serum TNF-α and IL-6 were also detected by ELISA and dopamine, norepinephrine, serotonin in the brain were analyzed by HPLC.Results （ 1 ） Morris water maze test showed, the retention time of the aged mouse model control group was significantly longer than that of the young mouse model eontrol group （P〈0.05）. The retention time of the artemisinin low dose group and the artemisinin high dose group was significantly shorter than that of the aged mouse model control group （P〈 0.05）. In the ninth days of the reverse reeessive platform experiment, the retention time of the artemisinin low dose group （（50.1＋19.9） s） and the artemisinin high dose group （（43.2±17.6） s） was significantly shorter than that of the aged mouse model control group （（66.1±29.1） s ,P〈0.05）. （2） Serum inflammatory factors test showed, the level of IL-6 and TNF-α in the artemisinin low dose group （ IL-6 ： （ 28.4 ± 4.3） pg/ml,TNF-α： （51.8±8.2） pg/ml） and the artemisinin high dose group（ IL-6 ：（17.6±2.3） pg/ml, TNF-α ： （38.6±12.5） pg/ml） were significantly lower than those in aged mouse model control group（ IL-6 ： （36.12-＋7.98）pg/ml） ,TNF-α ：（67.32±10.27） pg/ml,P〈0.05）. （3） Neurotransmitter content test in the brain showed, the content of DA（ （19.96±3.89） mmol/ml） and 5-HT（（5.73±0.93）mmol/ml） in low dose artemisinin group was higher than that in aged mouth model control group. The eontent of DA（（26.13±5.66） mmol/ml） , NE（ （16.31±2.69） mmol/ml） and 5-HT（（8.03±1.93） mmol/ml） in high dose artemisinin group was higher than that in aged mouth model group （ DA （13. 96 ± 3. 89 ） mmol/ml, NE（8.73±2.16） mmol/ml,5-HT （ 3.82± 1.09） mmol/ml, all P〈0.05）. Conclusion Artemisinin can improve the ability of learning and memory in aged mice. The mechanism may be related to inhibiting the inflammation and promoting the level of neurotransmitters in the brain of aged iniee.