黄芩苷对脑小血管病模型大鼠认知功能及脑内血管内皮生长因子和内皮抑素表达水平的影响

doi:10.13481/j.1671-587x.20190519

摘要/Abstract

摘要： 目的：探讨黄芩苷对脑小血管疾病模型大鼠认知功能及脑内血管内皮生长因子（VEGF）和内皮抑素（ES）表达的影响，阐明其作用机制。方法：采用同种系微栓子体外注入法复制脑小血管疾病大鼠模型，共48只，造模成功后大鼠随机分为模型组、低剂量（50 mg·kg^-1）黄芩苷组和高剂量（100 mg·kg^-1）黄芩苷组，每组16只，并以假手术大鼠作为对照组（n=16）。造模后次日开始给药，各组大鼠分别于制模7、14和28 d时采用Morris水迷宫实验检测学习记忆功能。采用RT-PCR法和蛋白印迹法检测大鼠脑组织中VEGF和ES mRNA和蛋白表达水平，HE染色观察各组大鼠大脑海马组织形态表现，免疫组织化学法检测各组大鼠大脑海马组织中VEGF和ES蛋白的表达。结果：与对照组比较，模型组大鼠7、14和28d Morris水迷宫逃避潜伏期明显延长（P<0.01），穿越平台次数明显减少（P<0.05或P<0.01）；与模型组比较，低和高剂量黄芩苷组大鼠7、14和28 d Morris水迷宫逃避潜伏期明显缩短（P<0.01），穿越平台次数明显增加（P<0.05或P<0.01）。与对照组比较，模型组大鼠大脑组织中VEGFmRNA和蛋白表达水平明显降低（P<0.05或P<0.01），ES mRNA和蛋白表达水平明显升高（P<0.05或P<0.01）；与模型组比较，低和高剂量黄芩苷组大鼠大脑海马区VEGFmRNA和蛋白的表达水平升高（P<0.05或P<0.01），ESmRNA和蛋白表达水平降低（P<0.05或P<0.01）。结论：黄芩苷可使脑小血管疾病模型大鼠逃避潜伏期缩短，病理改变减缓，对脑组织认知功能起到修复作用，且可降低脑组织中VEGF表达水平，增加ES表达水平，对脑组织起到保护作用。

关键词: 黄芩苷, 脑小血管疾病, 血管内皮生长因子, 内皮抑素, 认知功能, Morris水迷宫

Abstract: Objective:To explore the effects of baicalin on the cognitive function and the expression of vascular endothelial growth factor (VEGF), and endostatin(ES) in the brain tissue of the cerebral small vessel disease model rats, and to clarify their mechanisms. Methods:The rat models of cerebellar small vessel disease were duplicated by in vitro implantation of allogeneic microemboli. After successfully modeling, 48 model rats were randomly divided into model group, low dose(50 mg·kg^-1) of baicalin group, and high dose (100 mg·kg^-1) of baicalin group(n=16);On and the sham operation rats were used as control group(n=16).On the first day after modeling, the rats in each group were given drugs,and the learning and memory function of the rats in various groups were detected by Morris water maze experiment at 7, 14, and 28 d after modeling, respectively. The expression levels of VEGF and ES mRNA and protein in the brain tissue of the rats in various groups were detected by RT-PCR and Western blotting methods, and the morphology of the hippocampus tissue of the brain of the rats in various groups were observed by HE staining; the expressions of VEGF and ES proteins in the hippocampus tissue of the brain of the rats in various groups were detected by immunohistochemistry. Results:Compared with control group, the escape latency in Morris water maze of the rats in model group was significantly prolonged(P<0.01), the number of crossing the platform was significantly reduced (P<0.01), the brain tissue lesion was severe, the expression levels of VEGF mRNA and protein in brain tissue were significantly decreased (P<0.01), and the expression levels of ES mRNA and protein were significantly increased (P<0.01). Compared with model group, the escape latency in Morris water maze of the rats in high dose of baicalin group was significantly shortened(P<0.01), the number of crossing the platform was significantly increased(P<0.01), the degree of brain tissue lesion was alleviated, the expression levels of VEGF mRNA and protein in brain tissue were significantly increased(P<0.01), and the expression levels of ES mRNA and protein were significantly decreased (P<0.01). Conclusion:Baicalin can reduce the escape latency, improve the pathological changes, and repaire the cognitive function of brain tissue; it can decrease the VEGF expression level and increase the expression lvels of ES in the brain tissue of the cerebral small vessel disease model rats, and plays a protective role in the brain tissue.

Key words: baicalin, cerebral small vessel disease, vascular endothelial growth factor, erndostatin, cognitive function, morris water maze

中图分类号:

R-332

刘恒, 孙凡, 徐倩倩, 高燕军, 马征, 窦志杰. 黄芩苷对脑小血管病模型大鼠认知功能及脑内血管内皮生长因子和内皮抑素表达水平的影响[J]. 吉林大学学报(医学版), 2019, 45(05): 1080-1085.

LIU Heng, SUN Fan, XU Qianqian, GAO Yanjun, MA Zheng, DOU Zhijie. Effects of baicalin on cognitive function and expression levels of vascular endothelial growth factor and endostatin in cerebral small vessel disease model rats[J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1080-1085.

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