目的 采用D-半乳糖结合半高脂饲料联合应用构建痰浊阻窍型老龄认知功能障碍大鼠模型,观察和探讨涤痰汤对模型大鼠空间认知能力、海马神经元数量及树突棘密度的影响.方法 将13月龄SD大鼠随机分为老龄对照组、老龄认知障碍模型组(简称模型组)、西药组、涤低剂量组、涤高剂量组,另设3月龄大鼠为青年对照组.采用颈部皮下注射D-半乳糖8周,后4周加用半高脂饲料喂食的方法建立老龄认知障碍大鼠模型.西药组、涤低剂量组、涤高剂量组分别给予盐酸多奈哌齐片(0.9 mg/kg)、涤痰汤(4.275 g/kg)、涤痰汤(8.550 g/kg)灌胃4周,模型组、老龄对照组、青年对照组给予等容积蒸馏水灌胃.采用Morris水迷宫实验检测各组大鼠空间认知能力,尼氏染色观察大鼠海马神经元数量,Golgi染色分析海马神经元树突棘的改变.结果 老龄对照组与青年对照组的逃避潜伏期有显著性差异(P<0.05);与老龄对照组相比,模型组大鼠潜伏期明显延长(P<0.01);与模型组相比,涤高剂量组、西药组潜伏期明显缩短(均P<0.01)、涤低剂量组潜伏期亦缩短(P<0.05);西药组与涤高、涤低剂量组间的差异无统计学意义.青年对照组与老龄对照组海马神经元数量无显著性差异,但老龄对照组神经元树突棘密度降低(P<0.05);与老龄对照组相比,模型组海马神经元数量、神经元树突棘密度均降低,差异有统计学意义(均P<0.05);与模型组相比,涤高剂量组与西药组神经元数量、树突棘密度均增加(均P<0.05)、低剂量组变化不明显.结论 D-半乳糖结合半高脂饲料联合造模方法可造成大鼠认知功能障碍,表现为模型大鼠空间认知能力显著降低,海马组织神经元数量减少、神经元树突棘数量降低.涤痰汤能显著提高模型大鼠空间认知能力,保护海马组织神经元,改善突触可塑性.%Objective To explore the effect of Ditan Decoction on the spatial cognitive ability,the number of hippocampal neurons and the density of dendritic spines in aged cognitive impairment rat models of "phlegm turbidity" established by combining the use of D-galactose and semi-high-fat diet feeding.Methods Thirteen-month-old SD rats were randomly divided into aged control group,aged cognitive impairment model group(model group),western medicine group,low-dose Chinese medicine group,high-dose Chinese medicine group.Some other 3-month-old rats were selected as young control group.By subcutaneously injecting D-galactose on the neck of rats for 8 weeks,and adding semi-high-fat diet for the latter 4 weeks,we established the "phlegm turbidity"rat model of aged cognitive dysfunction.Rats in western medicine group,low-dose and high-dose Ditan Decoction group were treated with donepezil hydrochloride tablets(0.9 mg/kg),Ditan Decoction(4.275 g/kg),and Ditan Decoction(8.550 g/kg)respectively by gavage for 4 weeks.The model group,aged and young control groups received equal volume of distilled water.spatial cognitive abilities of rats were detected by the Morris water maze test.The effect of Ditan Decoction on the number of hippocampal neurons in rats was examined by Nissl staining.Then,by using Golgi staining combined with Imaris software,the effect of Ditan Decoction on the dendritic spine density of hippocampal neurons was measured and analyzed.Results The escape latency was significantly increased in aged control group compared with the young control group(P<0.05).It was significantly longer in the model group compared with the aged control group(P<0.01).The escape latency was significantly shortened in the high-dose Ditan Decoction group and western medicine group as compared with the model group(P<0.01).Such period in low-dose group was also shortened(P<0.05).There was no significant difference in the escape latency between the western medicine group and each Ditan Decoction group.The number of neurons in hippocampal tissues in aged control group was similar to that in the young control group,but the dendritic spine density was markedly decreased in aged control group(P<0.05).The number of hippocampal neurons and the density of dendritic spines were significantly decreased in the model group relative to the aged control group(P<0.01).They were much greater in both the high-dose Ditan Decoction group and western medicine group than in the model group(P<0.05).Conclusion Use of D-galactose and semi high fat diet combining can cause the cognitive dysfunction in aged rats.The spatial cognitive ability in those rats is significantly impaired,and the number and the dendritic spine density of hippocampal neurons are profoundly reduced.Ditan Decoction can significantly improve the spatial cognitive ability,and protect the neurons and synaptic structure in the hippocampus of the model rats.
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