脑通胶囊对VD大鼠海马NMDA受体 mRNA表达及锥体细胞的影响

目的:观察脑通胶囊对血管性痴呆(VD)大鼠学习记忆、海马N-甲基-D-天冬氨酸(NMDA)受体及锥体细胞的影响.方法:随机抽取大鼠19只作为假手术组,其余采用改良的四血管法(4-VO)制备VD模型并随机分为模型组、尼莫地平组( 12 mg·kg-1·d-1)、脑通胶囊高剂量组(1 200 mg· kg-1·d-1)、脑通胶囊中剂量组(600 mg·kg-1·d-1)、脑通胶囊低剂量组(300mg·kg-1·d-1).Morris水迷宫测定各组大鼠学习记忆能力,实时荧光定量PCR检测NMDA受体1亚基和2B亚基mRNA的表达情况,光镜观察海马CA1区锥体细胞形态及数量变化.结果:与模型组比较,脑通胶囊高、中剂量组逃避潜伏期缩短(P＜0.01),穿越原平台次数增加(P＜0.01,P＜0.05),NMDA受体1亚基mRNA表达降低(P＜0.01),2B亚基mRNA表达升高(P＜0.01,P＜0.05)；海马CA1区锥体细胞形态未见明显病变现象,锥体细胞数量增多,锥体细胞丢失比率减少.与尼莫地平组比较,脑通胶囊高、中剂量组穿越原平台次数增加(P＜0.01),NMDA受体1亚基mRNA相对表达量降低(P＜0.01),高剂量组NMDA受体2B亚基mRNA相对表达量增加(P＜0.05),CA1区锥体细胞增多(P＜0.01).结论:脑通胶囊可降低海马NMDA受体1亚基mRNA的表达,提高2B亚基mRNA的表达,减轻海马CA1区锥体细胞损伤,减少锥体细胞丢失比率,从而改善VD大鼠学习记忆能力,这可能是其治疗VD的作用机制之一.

Effect of Naotong Capsule on the NMDA Receptors and Pyramidal Cells in Hippocampus of Vascular Dementia Model Rats

Objective:To observe the effects of Naotong Capsule on N-methyl-D-aspartic acid receptor(NMDA) receptors and pyramidal cells in hippocampus of vascular dementia(VD) model rats.Method:Nineteen rats were taken at random into sham group,the rest were VD models established by modified Pulsinelli 4 vascular occlusions method(4-VO) and were randomly divided into model group,nimodipine group(12 mg·kg-1·d-1),Naotong Capsule large-dose group(1 200 mg·kg-1·d-1),Naotong Capsule middle-dose group(600 mg·kg-1·d-1),and Naotong Capsule low-dose group(300 mg·kg-1·d-1).Morris water maze was used to test learning and memory abilities of rats.The mRNA expression level of NMDA receptors(subunit 1 and 2B) were determined by the Real-time Quantitative PCR.And the morphology and number of neurons in CA1 region of the hippocampus were observed by light microscope.Result:Compare to the model group,the escape time was shortened(P<0.01),times of spanning the previous platform increased(P<0.01,P<0.05),the mRNA expression level of subunit 1 decreased(P<0.01) and the mRNA expression level of subunit 2B increased(P<0.01,P<0.05),pyramidal cells showed no obvious pathogenesis and more pyramidal cells with less pyramidal cells loss rate were found in Naotong Capsule large-dose and middle-dose treatment group.Compare to the Nimodipine group,times of spanning the previous platform increased(P<0.01),the mRNA expression level of subunit 1 decreased(P<0.01) in Naotong Capsule large-dose and middle-dose treatment group,and the mRNA expression level of subunit 2B increased(P<0.05),the number of neurons in CA1 region of the hippocampus increased(P<0.01) in Naotong Capsule large-dose treatment group.Conclusion: Naotong Capsule can improve learning and memory abilities of VD rats by decreasing the mRNA expression level of subunit 1,increasing the mRNA expression level of subunit 2B of NMDA receptor and by decreasing pyramidal cells injury and loss rate in CA1 region of the hippocampus,which may be one of the therapeutic mechanisms of VD.