白藜芦醇上调阿尔茨海默病模型大鼠海马组织N-甲基-D-天冬氨酸受体1及蛋白激酶C基因和蛋白的表达  

Resveratrol upregulates the gene and protein expressions of N-methyl-D-aspartate receptor 1 and protein kinase C in the hippocampus in Alzheimer′s disease rats

作　　者：张玉森 董瑞瑞 杨倩 张禄平 李静 赵海峰 Zhang Yusen;Dong Ruirui;Yang Qian;Zhang Luping;Li Jing;Zhao Haifeng(Department of Nutrition and Food Hygiene,School of Public Health,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学公共卫生学院营养与食品卫生学教研室,太原030001

出　　处：《卫生研究》2019年第2期269-272,278,共5页Journal of Hygiene Research

基　　金：国家自然科学基金(No.81472984;81001245);2013年度山西医科大学科技创新基金(No.01201301);山西医科大学2017年大学生创新创业校级基金(No.20170372)

摘　　要：目的探讨白藜芦醇对阿尔茨海默病(Alzheimer’s disease, AD)模型大鼠海马组织N-甲基-D-天冬氨酸受体1(N-methyl-D-aspartate receptor, NMDAR1)及蛋白激酶C(protein kinase C, PKC)基因和蛋白表达的影响。方法将60只Wistar雌性大鼠随机分为6组,分别为:假手术对照组,AD模型对照组,白藜芦醇低、中、高剂量(20、40和80 mg/kg)干预组,0.8 mg/kg戊酸雌二醇阳性对照组。采用去卵巢合并腹腔注射100 mg/kg D-半乳糖制备AD大鼠模型,同时白藜芦醇灌胃干预12周。干预后用实时荧光定量PCR检测大鼠海马组织NMDAR1和PKC基因的表达,用Western Blot检测NMDAR1总蛋白、磷酸化蛋白和PKC蛋白的表达。结果与假手术组相比,模型组NMDAR1及PKC基因和蛋白的表达明显下调(P<0.05);与模型组相比,白藜芦醇各剂量组NMDAR1和PKC基因的表达显著上调(P<0.05),以80 mg/kg组最为明显(P<0.01),对NMDAR1基因上调程度与戊酸雌二醇相当,40和80 mg/kg干预组p-NMDAR1/NMDAR1比值明显增加(P<0.05或P<0.01),PKC蛋白表达明显上调(P<0.05或P<0.01),与戊酸雌二醇效果相当。结论白藜芦醇上调NMDAR1及PKC基因的表达并且促进NMDAR1蛋白磷酸化和PKC蛋白的表达,可能是其改善AD模型大鼠记忆的机制之一。OBJECTIVE To investigate the effects of resveratrol(Res)on N-methyl-D-aspartate receptor(NMDAR1)and protein kinase C(PKC)expressions in the hippocampus in Alzheimer's disease(AD)rats.METHODS The model of AD was induced by ovariectomy combined intraperitoneal injection of D-galactose(100 mg/kg).Thirty-Six female Wistar rats were randomly divided into 6 groups inculding Sham control group,AD model group,Res low dose group(20 mg/kg),Res middle dose group(40 mg/kg),Res high dose group(80 mg/kg group)and estrogen replacement therapy(ERT)group.The genes of NMDAR 1 and PKC were detected by real-time PCR.NMDAR 1 total protein,p-NMDAR 1 protein and PKC protein were checked by Western blot.RESULTS Compared with the Sham control group,the gene expressions and the protein expressions of NMDAR1 and PKC in the model group were decreased(P<0.05).Moreover,compared with the model group,genes of NMDAR 1 and PKC in the 3 Res dose groups were significantly increased(P<0.05 or P<0.01).The elavated levels of genes of NMDAR1 and PKC in ERT group were similar to the Res 80 mg/kg group(P<0.01).p-NMDARI/NMDAR 1 and the protein expressions of PKC were also significantly increased in Res 40 mg/kg group and Res 80 mg/kg group as well as in ERT group(P<0.05 or P<0.01).CONCLUSION Up-regulating the gene and protein expressions of p-NMDAR1/NMDAR 1 and PKC may be one of the mechanisms of improvement of Res on the memory in AD rats.

关 键 词：阿尔茨海默病 白藜芦醇 N-甲基-D-天冬氨酸受体1 蛋白激酶C 

分 类 号：Q593.2[生物学—生物化学] R338.64[医药卫生—人体生理学]