脑通汤对VD大鼠海马CA1区ICAM-1、EBA及GFAP蛋白表达的影响

Effect of Nao Tong Decoction on the ICAM-1 and EBA Expression in the Hippocampus Area of Vascular Dementia Rats

目的:观察脑通汤对血管性痴呆大鼠学习记忆能力以及海马CA1区细胞间黏附分子(ICAM-1)、内皮屏障抗原(EBA)和胶质纤维酸性蛋白(GFAP)表达的影响。方法:除假手术以外的其他组大鼠采用改良的4-VO法制备大鼠模型,造模1周后予药物灌胃治疗,1次/d,共灌胃4周。灌胃治疗结束后Morris水迷宫检测大鼠学习记忆能力,免疫组化法检测海马区CA1区ICAM-1、EBA和GFAP表达水平。结果:模型组大鼠逃避潜伏期明显延长,ICAM-1表达明显增加、EBA表达减少、GFAP表达显著增加,与假手术组比较具有显著差异(P<0.01)。脑通汤大、中剂量组均可显著缩短大鼠逃避潜伏期,可显著降低ICAM-1、GFAP表达,促进EBA表达,与模型组比较具有显著差异(P<0.01)。结论:脑通汤对VD大鼠学习记忆能力减退具有防治作用,其机制可能通过抑制ICAM-1、GFAP表达,促进EBA表达,改善血管内皮细胞、星形胶质细胞以及血脑屏障的损伤,从而减轻脑缺血对神经血管单元(NVU)的损害。

Objective：To observe the effects of Naotong decoction on the ability of learning and memory, and the levels of intercellular adhesion molecule 1 （ICAM-1）, endothelial barrier antigen （EBA）,glial fibers acidic protein （GFAP） expression of hippocampal CA1 area in rats with vascular dementia, and to explore the possible therapeutic mechanism. Method： Ninety female SD rats were randomly divided into six groups： ①pseudo-operation group ②model group③Donepezil HCL group ④Naotong decoction high dose group⑤Naotong decoction moderate dose group⑥Naotong decoction low dose group, Fifteen rats contained in each group. Model making was performed on the rats in addition to the pseudo-operation group by modified Pulsinelli 4 vascular occlusions method （4VO）. One week after the surgery, the rats underwent gavage treatment for 4 weeks, one time a day. After the treatment, the Morris Water Maze were used to test the ability of learning and memory in vascular dementia model rats, mmunohistochemical method to detect the ICAM - 1, EBA and GFAP protein expression in hippocampal CA1 area. Result： Compared to pseudo-operation group, the model group escape time were increased and the times of spanning the previous platform were reduced, the expression of ICAM-1 .GFAP were reduced,and the expression of EBA were decreased （P〈0.01）. Compared to model group, escape time were reduced, the levels of ICAM-1 .GFAP were decreased, the expression of EBA were increased in the Naotong decoction high and moderate dose groups （P〈0.01）. Conclusion： Naotong Decoction can obviously prevent learning and memory deficit of VaD rats, and the mechanism might relate to reduce the expression of ICAM-1 and GFAP protein, improve the EBA expression, relieve the damage to cerebral microvascular endothelial cells and astrocytes , and thus reduce ischemic damage to nerve vascular unit.