生姜提取物对Alzheimer病大鼠认知功能障碍的作用及其机制

Effect and its mechanism of ginger root extract on cognitive dysfunction in rats with Alzheimer disease

目的研究生姜提取物(GRE)对Alzheimer病(AD)大鼠认知功能障碍的作用及其机制。方法60只SD大鼠随机分为假手术组、AD对照组、GRE低剂量组、GRE中剂量组、GRE高剂量组和石杉碱甲组,每组10只大鼠。AD大鼠模型采用脑室注射β淀粉样蛋白Aβ25-35及氯化铝溶液灌胃法制作。造模成功后,AD对照组大鼠给予生理盐水,其余各组AD大鼠给予相应药物灌胃20 d。采用Morris水迷宫空间探索试验检测大鼠学习记忆能力。采用脑组织HE染色、尼氏染色计数神经元和尼氏小体数。用免疫组化染色和酶联免疫吸附法检测脑组织内代谢因子超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、核因子-κB(NF-κB)及白介素1β(IL-1β)的表达及血丙二醛(MDA)水平。结果与假手术组比较,AD对照组、GRE低剂量组、GRE中剂量组水迷宫试验的潜伏期明显延长,海马神经元及其尼氏小体数明显减少,SOD、CAT表达明显降低,NF-κB、IL-1β表达及血MDA水平明显增高(均P<0.05)。与AD对照组、GRE低剂量组、GRE中剂量组比较,GRE高剂量组和石杉碱甲组水迷宫试验的潜伏期明显缩短,海马神经元及其尼氏小体数增多,SOD、CAT表达明显增高,NF-κB、IL-1β表达及血MDA水平显著降低(均P<0.05)。结论大剂量GRE可提高AD大鼠学习记忆能力。其机制可能与GRE减轻脑组织损害、抗氧自由基和抑制炎症因子的表达有关。

Objective To investigate the effect and its mechanism of ginger root extract （GRE） on cognitive dysfunction in rats with Alzheimer disease （AD）. Methods Sixty SD rats were randomly divided into sham operation group, AD centrol group, GRE low dose group, GRE medium dose group, GRE high dose group and huperzine A group, with 10 rats in each group. AD rat models were established by intracerebroventricular injection of A[325_35 and intragastric administration of Alumina solution. After that, rats in AD control group were given saline by intragastric administration, and the other AD rats were given corresponding drug for 20 d. The Morris water maze was used to evaluate the ability of learning and memory of rats. The number of neurons and Nissl bodies were counted by using HE and Nissl staining of brain tissue. The metabolic factors as superoxide dismutase （SOD）, catalase （CAT）, nuclear factor-KB （NF-KB）, interleukin-113 （IL-113） and malondialdehyde （MDA） were determined by immunohistochemical method and Enzyme-linked immunosorbent assay method. Results Compared with sham operation group, the latency of water maze test was significantly prolonged, the hippocampal neurons and their nissl bodies as well as the expression of SOD and CAT were significantly decreased, the expression of NF-KB and IL-113 and the level of MDA were significantly increased in AD centrol group, GRE low dose group and GRE medium dose group （all P 〈 O. 05）. Compared with AD centrol group, GRE low dose group and GRE medium dose group, the latency of water maze test was significantly shortened, the hippocampal neurons and their nissl bodies as well as the expression of SOD and CAT were significantly increased, the expression of NF-KB and IL-113 and the level of MDA were significantly decreased in GRE high dose group and huperzine A group （ all P 〈0. 05 ）. Conclusions High dose of GRE can improve the learning and memory ability of AD rats. Its mechanism may be related with the reducing of brain tissue injury, antioxygen free radical and inhibiting the expression of inflammatory factors of GRE.