摘要
目的观察淫羊藿苷(Ica)对Aβ_(25-35)致阿尔采末病(AD)大鼠的空间学习记忆能力障碍的改善作用及可能机制。方法 SD大鼠43只,随机分为对照组(n=13)、模型组(n=15)及Ica(120 mg·kg^(-1))组(n=15),每日灌胃给药1周后,右侧海马内注射Aβ_(25-35)10μg制备AD模型,制模后继续给药3周。Morris水迷宫检测大鼠空间学习记忆能力,ELISA检测大鼠海马肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)蛋白的含量,Western blot检测半胱氨酸天冬氨酸蛋白酶(caspase-3)蛋白的表达,real time RT-PCR检测海马TNF-α,IL-6和caspase-3 mRNA的表达。结果水迷宫结果表明,与对照组比较,模型组大鼠平均逃避潜伏期明显延长,进入平台次数、原平台象限滞留时间百分比及原平台象限运动距离百分比均显著降低(P<0.05);与模型组比较,Ica组大鼠的平均逃避潜伏期明显缩短,进入平台次数、原平台象限滞留时间百分比及原平台象限运动距离百分比均明显增加(P<0.05)。模型组大鼠海马中的TNF-α和IL-6含量及caspase-3蛋白表达明显高于对照组(P<0.05);Ica组大鼠海马中的TNF-α和IL-6含量及caspase-3蛋白表达均显著降低(P<0.05),TNF-α,IL-6及caspase-3的mRNA表达也显著低于模型组(P<0.05)。结论 Ica可能通过抑制炎症因子TNF-α,IL-6以及凋亡基因caspase-3的表达改善Aβ_(25-35)诱导的AD大鼠空间学习记忆能力。
AIM To study the effects of icariin （Ica） on spatial learning and memory in Aβ25-35 induced Alzheimer＇ s disease （AD） rats and investigate its＇ mechanisms. METHODS The SD rats were randomly divided into control group （n = 13）, model group （n = 15） and Ica 120 mg.kg^-1 group （n = 15）. The AD model was induced by injecting Aβ25-35 10 μg into the right hippocampus. Ica was given orally daily for 1 week before and 3 weeks after Aβ25-35 administration. The Morris Water Maze was used to observe the spatial learning and memory of rats. The protein levels of TNF-α and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA） and the caspase-3 protein expression was assayed by western blot. The mRNA levels of TNF-α, IL-6 and caspase- 3 in hippocampus were determined by real time RT- PCR. RESULTS In place navigation training, the latency of rats was increased significantly in the model group （vs. control group, P 〈 0.05） and decreased in Ica group （vs. model group, P 〈 0.05）. In spatial probe test, the times of passing platform, percent of residence time and swim distance on original platform quadrant were decreased significantly in the model group （vs. control group, P 〈 0.05）, but increased in Ica 120 mg.kg^-1 group （vs. model group, P 〈 0.05）. In addition, Ica decreased the expression of TNF-α, IL-6 and caspase-3 mRNA and proteins levels in hippocampus （vs. model group, P 〈 0.05）. CONCLUSION Ica can improve the spatial learning and memory ability in Aβ25-35 induced AD rats, and the mechanism may be related with the inhibition of cytokines TNF-α, IL-6 and apoptotic gene caspase-3.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2013年第10期833-837,共5页
Chinese Journal of New Drugs and Clinical Remedies
基金
“973”前期专项(2011CB512009)
国家自然科学基金项目(81160400)
贵州省科技厅(黔科合J字[2009]2147号)
贵州省中医药管理局项目(QZYY2010,D-274)
