生姜提取物对染铝毒大鼠学习记忆功能和神经细胞结构的影响及其可能作用机制  

Effect of ginger root extract on learning and memory function and nerve cell structure in rats exposed to aluminum and its possible mechanism

作　　者：谢晶[1] 蒋小云 覃黎黎 韦益宇 郑艳艳[1] 杨莉[2] XIE Jing;JIANG Xiaoyun;QIN Lili;WEI Yiyu;ZHENG Yanyan;YANG Li(Institute for Occupational Health and Toxicity Evaluation,Guangxi Zhuang Autonomous Region Institute for the Prevention and Treatment of Occupational Diseases,Nanning 530021,Guangxi,China;School of Public Health,Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西壮族自治区职业病防治研究院职业卫生与毒性评价所,广西南宁市530021 [2]广西医科大学公共卫生学院,广西南宁市530021

出　　处：《广西医学》2024年第5期713-720,共8页Guangxi Medical Journal

基　　金：广西壮族自治区卫生健康委员会自筹经费科研课题(Z20180271)。

摘　　要：目的分析生姜提取物(GRE)对铝染毒大鼠学习记忆功能及神经细胞结构的影响,并基于钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)、神经元型一氧化氮合酶(nNOS)、蛋白激酶C(PKC)探讨其可能的作用机制。方法将36只SD雄性大鼠随机分为空白对照组、铝染毒组、临床药物组、低剂量GRE(L⁃GRE)组、中剂量GRE(M⁃GRE)组、高剂量GRE(H⁃GRE)组,每组6只大鼠。空白对照组大鼠自由饮用不含氯化铝的饮用水,其余组大鼠饮用含10 mg/mL结晶氯化铝的饮用水。3个月后给予空白对照组和铝染毒组大鼠灌胃生理盐水,临床药物组大鼠灌胃盐酸多奈哌齐溶液,分别给予L⁃GRE组、M⁃GRE组、H⁃GRE组大鼠灌胃100 mg/kg、200 mg/kg、400 mg/kg GRE溶液。持续干预4周后,采用Morris水迷宫实验评估大鼠的学习记忆功能,通过HE染色观察大鼠海马组织形态变化,分别采用实时荧光定量PCR和Western blot检测大鼠海马组织CaMKⅡ、nNOS、PKC mRNA和蛋白表达水平。结果(1)与空白对照组相比,铝染毒组大鼠的逃避潜伏期延长且穿越平台次数减少(P<0.05),海马组织的神经细胞皱缩,神经细胞数量明显减少,CaMKⅡ、nNOS、PKC的mRNA表达水平及nNOS、PKC的蛋白表达水平降低(P<0.05)。(2)与铝染毒组比,L⁃GRE组、M⁃GRE组和H⁃GRE组大鼠的逃避潜伏期缩短,临床药物组、M⁃GRE组、H⁃GRE组大鼠的穿越平台次数增加(P<0.05);各给药组大鼠海马组织病理形态有不同程度的改善;临床药物组大鼠的CaMKⅡ、nNOS和PKC mRNA表达水平升高,各剂量GRE组大鼠nNOS和PKC mRNA和蛋白表达水平升高(P<0.05)。(3)与临床药物组相比,M⁃GRE组和H⁃GRE组大鼠的逃避潜伏期,以及各剂量GRE组的穿越平台次数和目标象限停留时间差异无统计学意义(P>0.05);各剂量GRE组大鼠海马组织病理形态改善程度更为明显;M⁃GRE组、H⁃GRE组大鼠的nNOS、PKC蛋白表达水平升高,L⁃GRE组大鼠的nNOS蛋白表达水平升�Objective To analyze the effect of ginger root extract(GRE)on learning and memory function and nerve cell structure in rats exposed to aluminum,and to explore its possible mechanism based on calmodulin⁃dependent protein kinaseⅡ(CaMKⅡ),neuronal nitric oxide synthase(nNOS)and protein kinase C(PKC).Methods A total of 36 SD male rats were randomly assigned to blank control group,aluminum exposed group,clinical drug group,low⁃dose GRE group(L⁃GRE group),medium⁃dose GRE group(M⁃GRE group)or high⁃dose GRE group(H⁃GRE group),with 6 rats in each group.Rats in the blank control group freely drank water without aluminium chloride,and rats in the remaining groups drank water containing 10 mg/mL crystallization of aluminium chloride.After 3 months,intragastric administration of normal saline was given to the blank control group and the aluminum exposed group,whereas intragastric administration of donepezil hydrochloride solution was given to the clinical drug group;in addition,intragastric administration of 100 mg/kg,200 mg/kg,and 400 mg/kg GRE solutions was given to the L⁃GRE,M⁃GRE,and H⁃GRE groups,respectively.After 4 weeks of continuous intervention,Morris water maze test was used to evaluate learning and memory function of rats.The morphological changes of hippocampus tissues in rats were observed by the HE staining.The mRNA and protein expressions of CaMKⅡ,nNOS,and PKC in hippocampus tissues of rats were detected by employing the real⁃time fluorescent quantitative PCR and Western blot,respectively.Results(1)Compared with the blank control group,rats of the aluminum exposed group exhibited a prolong period of escape latency,and decreased frequency of platform crossing(P<0.05),as well as presented as shriveled nerve cells in hippocampus tissues,and significantly reduced number of nerve cells;in addition,the aluminum exposed group yielded decreased mRNA expressions of CaMKⅡ,nNOS,and PKC,and decreased protein expressions of nNOS and PKC(P<0.05).(2)Compared with the aluminum exposed group,the L�

关 键 词：铝染毒 生姜提取物 学习记忆 神经细胞结构 钙调蛋白依赖性蛋白激酶Ⅱ 神经元型一氧化氮合酶 蛋白激酶C 大鼠 

分 类 号：R285[医药卫生—中药学]