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目的:探讨中药提取物地黄寡糖(rehmannia glutinosa oligosaccharides,ROS)对血管性痴呆大鼠海马CA1区神经细胞凋亡及相关蛋白表达的影响。方法:选用SD成年大鼠,随机分为伪手术组、模型组和地黄寡糖高、低剂量组(9.0,45 g.kg-1.d-1)。采用双侧颈总动脉缺血再灌注法制作血管性痴呆大鼠模型,采用行为学评分法评价大鼠的行为学障碍程度,HE染色法观察大鼠海马CA1区病理组织形态学变化,TUNEL法检测大鼠海马CA1区的神经元细胞凋亡情况,免疫组化法检测大鼠海马区凋亡相关蛋白B细胞淋巴瘤/白血病-2(Bcl-2),Bcl-相关x蛋白(Bax)的表达含量的变化,并检测大鼠海马组织匀浆中神经毒性氨基酸谷氨酸及海马组织和血清中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量。结果:ROS能够显著改善缺血再灌注型血管性痴呆的大鼠的行为学障碍,降低其行为学评分(P<0.01),减轻海马CA1区神经组织的病理性改变,降低神经元凋亡细胞比例(P<0.01),并显著升高血管性痴呆大鼠海马CA1区神经元细胞中Bcl-2蛋白表达(P<0.01)、降低Bax蛋白表达(P<0.01),Bcl-2/Bax显著升高,从而抑制了该区域神经元细胞的凋亡。此外,ROS给药能够显著减少血管性痴呆大鼠血清及海马组织中MDA的积累(P<0.01),提高SOD的活性(P<0.01),降低海马组织中谷氨酸的水平(P<0.01)。结论:ROS能够显著减少脑缺血再灌注损伤所致的大鼠海马CA1区神经元凋亡,其作用机制可能是通过调控Bcl-2/Bax相关蛋白的表达来实现的。此外与ROS减少组织中谷氨酸的水平和MDA的含量,提高SOD活性等,也提示ROS对血管性痴呆有一定的治疗作用。
Objective: To investigate the effect of rehmannia glutinosa oligosaccharides (ROS), a traditional Chinese medicine extract, on neuronal apoptosis and related protein expression in hippocampal CA1 area of vascular dementia rats. Methods: SD adult rats were randomly divided into sham operation group, model group and Rehmannia glutinosa high and low dose group (9.0,45 g.kg-1.d-1). The rat model of vascular dementia was established by bilateral carotid artery ischemia-reperfusion. The behavioral score was used to evaluate the degree of behavioral disorders. The morphological changes of hippocampal CA1 area were observed by HE staining. The apoptosis of hippocampal CA1 region was detected by immunohistochemistry. The expressions of Bcl-2, Bcl-x and Bcl-2 in hippocampus were detected by immunohistochemistry (SOD) and malondialdehyde (MDA) contents in the neurotoxic amino acids glutamic acid, hippocampus and serum of hippocampus tissue homogenates of rats. Results: ROS could significantly improve the behavioral disorders of rats with vascular dementia and reduce their behavioral scores (P <0.01), reduce the pathological changes in the hippocampal CA1 area and decrease the number of apoptotic neurons (P <0.01), and significantly increased the expression of Bcl-2 protein in hippocampal CA1 neurons of Vascular Dementia rats (P <0.01), and decreased the expression of Bax protein (P <0.01) Increased, thus inhibiting the area of neuronal apoptosis. In addition, administration of ROS significantly decreased MDA accumulation in serum and hippocampus of rats with vascular dementia (P <0.01), increased SOD activity (P <0.01) and decreased glutamate levels in hippocampus (P <0.01) . CONCLUSION: ROS can significantly reduce neuronal apoptosis in hippocampal CA1 region of rats induced by cerebral ischemia-reperfusion injury, and its mechanism may be through the regulation of Bcl-2 / Bax-related protein expression. In addition, ROS reduces the level of glutamate in the tissue and the content of MDA, and increases the activity of SOD. It also suggests that ROS has a certain therapeutic effect on vascular dementia.