脑通复方制剂对血管性痴呆模型大鼠海马神经元细胞外调节蛋白激酶表达的影响

Effect of Naotong compound recipe on the changes of ERK in the hippocampal neurons in vascular dementia rats

目的:探讨观察脑通复方制剂对拟血管性痴呆(VaD)模型大鼠海马神经元中分裂原激活的蛋白激酶(MAPK)信号转导系统细胞外调节蛋白激酶(ERK1/2)及其磷酸化(p-ERK1/2)表达的影响。方法:采用改良Pulsinelli四血管阻断法复制大鼠血管性痴呆模型,脑通复方制剂治疗后观察学习记忆能力,Western-blotting法测定海马神经元总ERK1/2及p-ERK1/2蛋白表达。结果:脑通复方制剂可缩短实验大鼠逃避潜伏期,增加跨越平台次数;假手术组、VaD模型组、脑通复方制剂组及多哌齐特(安立申)组的ERK1/2蛋白水平分别为(1.20±0.19)、(1.11±0.14)、(1.18±0.13)、(1.25±0.14),任意两组间比较,差异均无统计学意义(P>0.05);假手术组、VaD模型组、脑通复方制剂组及多哌齐特(安立申)组p-ERK1/2蛋白水平分别为(0.75±0.07)、(0.38±0.08)、(0.58±0.10)、(0.65±0.08),模型组与假手术组相比p-ERK1/2蛋白表达降低,差异有统计学意义(P<0.01);脑通复方制剂组和多哌齐特(安立申)组p-ERK1/2蛋白表达较模型组升高,差异有统计学意义(P<0.05,P<0.01)。大鼠海马组织p-ERKl/2与空间探索实验第1次到达平台区域时间呈负相关(r=-0.664,P<0.05),与穿越平台区域次数呈负相关(r=-0.579,P<0.05)。结论:脑通复方制剂对VaD大鼠空间学习记忆减退有明显防治作用,具有提高VaD大鼠海马组织中的p-ERK1/2的表达作用。

OBJECTIVE To observe the effect of Naotong compound recipe on the changes of extracellular signal regulated kinase（ERK and p-ERK） in the hippocampal neurons in vascular dementia （VaD） rat. METHODS The VaD model rats were established with modified 4 VO. All the experimental rats were divided into Naotong compound recipe, model, donepezil hydrochloride and sham operation groups. The protein levels of ERK1/2 in rat hippocampus were detected by Western-blot- ting. RESULTS The ERK1/2 protein levels in sham operation, model, Naotong compound recipe and donepezil hydrochloride group was （1.20± 0. 19）, （1.11 ± 0. 14）, （1.18± 0. 13）, （1.25 ± 0. 14）, respectively. There was no statistical difference be tween any two groups （P〈0. 05）. pERK1/2 protein in sham operation, model, Naotong compound recipe and donepezil hydrochloride group was （0. 75 ± 0.07）, （0.38 ± 0.08）, （0. 58 ± 0. 10）, （0. 65 ± 0.08）, respectively, p-ERKI/2 in model group was decreased compared to sham operation group, the difference being significant （P〈0. 01）. Naotong compound recipe and donepezil hydrochloride up regulated expression of p-ERK, the difference reached a significant level （P〈0.05, P〈0. 01 ）. The proteins of p-ERK1/2 were negative correlated with the time taken to reach the first cross platform located in the probe test （r = -0. 664,P〈0. 05） and the protein of p-ERK1/2 were also negative correlated with the escape latencies on the fourth day （r= - 0. 579,P〈0.05）. CONCLUSION Naotong compound recipe up-regulated expression of p-ERK and icnproved abili- ties of learning and memory of VaD rats.