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目的探讨白藜芦醇对阿尔茨海默病(Alzheimer′s disease,AD)模型大鼠海马组织中CaMKⅡ及PKA C-β基因表达的影响。方法鼠龄4~5个月健康雌性Wistar大鼠60只,按体质量随机分为假手术对照组(Sham control)、AD模型组(Model)、白藜芦醇低剂量(Res 20mg/kg)、中剂量(Res 40mg/kg)、高剂量(Res 80mg/kg)干预组及戊酸雌二醇组(ERT)。每组10只大鼠,对后5组大鼠行双侧卵巢摘除术,假手术组大鼠只切除双侧卵巢附近等体积的脂肪。术后一周开始给予干预,干预持续12周,取3只大鼠海马组织石蜡包埋切片进行HE染色检测海马组织神经细胞数量。利用Real-time PCR方法进行其余大鼠海马组织中CaMKⅡ及PKA C-β基因表达的检测。结果 (1)海马组织锥体细胞形态的改变:与假手术对照组比较,AD模型组大鼠海马锥体细胞排列稀疏、紊乱,细胞体积缩小,胞核固缩,胞浆浓缩、深染;白藜芦醇干预后细胞排列较整齐、均匀,结构清晰。(2)海马组织中CaMKⅡ及PKA C-β基因表达的改变:与对照组比较,模型组大鼠海马中CaMKⅡ及PKA C-β基因表达显著降低(P<0.05);与模型组比较,白藜芦醇干预组及ERT组大鼠海马中上述两个基因表达显著升高(P<0.05)。结论白藜芦醇可以升高AD模型大鼠海马组织中CaMKⅡ及PKA C-β基因的表达,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 on the expression of CaMK Ⅱ and PKA C-β in hippocampus of Alzheimer’s disease (AD) model rats. Methods Sixty healthy female Wistar rats aged 4 to 5 months were randomly divided into Sham control group, AD model group, Res 20 mg / kg group, , Medium dose (40 mg / kg), high dose (80 mg / kg) intervention group and estradiol valerate group (ERT). Each group of 10 rats, the latter 5 groups of rats underwent bilateral ovariectomy, sham-operated rats only resection of bilateral ovarian equal volume of fat. One week after the operation, intervention was given. The intervention lasted for 12 weeks. Three hippocampus tissues were paraffin-embedded for HE staining to detect the number of neurons in the hippocampus. Real-time PCR method was used to detect the expression of CaMKⅡ and PKA C-β in the remaining rat hippocampus. Results (1) The morphological changes of pyramidal cells in hippocampus: Compared with the sham operation control group, pyramidal cells in hippocampus of AD model group were sparse and disorderly arranged, the cell volume was reduced, the nuclei were pyknotic, cytoplasm was concentrated, After resveratrol intervention cells arranged more orderly, uniform, clear structure. (2) The changes of CaMKⅡand PKA C-βgene expression in hippocampus: Compared with the control group, the expression of CaMKⅡ and PKA C-βgene in the hippocampus of the model group was significantly decreased (P <0.05); compared with the model group, The expression of these two genes in hippocampus of rats treated with resveratrol and ERT was significantly increased (P <0.05). Conclusion Resveratrol can increase the expression of CaMK Ⅱ and PKA C-β in hippocampus of AD model rats, which may be one of the mechanisms to improve memory of AD model rats.