鹰嘴豆异黄酮提取物对阿尔茨海默病模型大鼠学习记忆能力及其海马内TNF-α、IL-6表达的影响

Effect of Isoflavone Extract from Cicer Arietinum on Learning Memory Abilities and Expressions of TNF-α and IL-6 in Hippocampus of Alzheimer’s Disease Model Rats

关键词:  鹰嘴豆异黄酮提取物  阿尔茨海默病  肿瘤坏死因子-α  细胞白介素-6  海马

Key words:  isoflavone extract from Cicer arietinum  Alzheimer’s disease  TNF-α  IL-6  hippocampus

摘要:

目的 探讨鹰嘴豆异黄酮提取物(CIE)对阿尔茨海默病(AD)炎症模型大鼠记忆能力的影响，并探讨其可能的作用机制。方法 采用脂多糖右侧海马注射制备AD模型，40只Wistar大鼠随机分为CIE高、中、低剂量组(100，50，25 mg·kg^-1)、模型组和对照组(生理盐水)，灌胃给药28 d后，采用Y-迷宫测试大鼠的学习记忆能力，采用免疫组化法检测大鼠海马内肿瘤坏死因子-α(TNF-α)和细胞白介素-6(IL-6)的表达。结果 与对照组比较，模型组大鼠学习记忆能力明显下降，尝试次数均明显增加(P<0.01)，TNF-α和IL-6的表达水平有显著提高(P<0.01)；经过灌胃给药不同剂量的CIE后，与模型组相比，大鼠学习记忆的尝试次数和TNF-α、IL-6的表达水平有不同程度的降低，并呈现一定的剂量依赖性，特别在中、高剂量组差异具有统计学意义(P<0.05或P<0.01)。结论 CIE对AD模型大鼠的学习记忆能力有明显的改善作用，其作用机制可能与抑制模型大鼠海马组织内TNF-α和IL-6的表达有关，进而抑制海马神经元的炎症反应。

Abstract:

OBJECTIVE To investigate the influence of isoflavone extract from Cicer arietinum(CIE) on learning memory abilities of rats with Alzheimer’s disease (AD) and discuss the possible mechanism of action. METHODS AD model rats were established by injection of lipopolysaccharides into the right hippocampus. Forty rats were allocated into five groups: high, middle and low-dose CIE group (100, 50, 25 mg·kg^-1), model group and control group (normal saline). After intragastrically administrated with different solution for 28 d, learning and memory abilities of rats were tested by Y-maze. The levels of TNF-α and IL-6 in rats’ hippocampus were detected by immunohistochemistry. RESULTS Compared with control group, the learning and memory abilities of model group rats decreased obviously with counts of attempts were significantly increased(P<0.01). The expressions of TNF-α and IL-6 in model group rats’ hippocampus improved significantly(P<0.01). After intragastrically administrated with different doses of CIE, the counts of attempts in learning and memory ability tests and expressions of TNF-α and IL-6 were lower than these in model group with a slightly dose-dependent manner. Especially in the middle-dose CIE group and high-dose CIE group, the differences were statistically significant (P<0.05 or P<0.01). CONCLUSION CIE can significantly improve the learning and memory abilities of AD model rats. Its mechanism may be related to inhibition of the expression of TNF-α and IL-6 in the AD rats’ hippocampus to restrain the inflammatory response.