黄芩苷对高原性小鼠脑损伤的影响及其机制研究  

Mechanism of Baicalin on High Altitude Cerebral Hypoxia-ischemia on Mice

作　　者：李园园[1] 任仲坤[1] 杨晖[2] 

机构地区：[1]昆明医科大学第一附属医院,昆明650032 [2]昆明医科大学生物医学工程中心,昆明650500

出　　处：《世界科学技术-中医药现代化》2015年第8期1693-1699,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：云南省科技厅-昆明医科大学联合专项项目(40210012):黄芩苷抗高原缺血性脑病所致轴索损伤的分子靶点的研究;负责人:李园园;云南省教育厅一般项目(K13201044):黄芩苷对小鼠视神经缺血性损伤保护作用机制的研究;负责人:杨晖

摘　　要：目的:探讨黄芩苷对高原性脑缺血缺氧致小鼠脑损伤的影响及相关作用靶点蛋白表达。方法:用water maze水迷宫作业测试筛选出50只昆明种小鼠,随机分为模型组、对照组、黄芩苷低、中、高剂量组(0.05、0.20、0.60 mg·kg-1),每组10只,检测受试小鼠的空间记忆和学习能力。用低压氧动物舱(模拟海拔4 000 m的高度)建立稳定的高原性脑缺血缺氧模型,检测小鼠海马组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性及丙二醛(MDA)含量的变化。应用蛋白印迹分析方法(western blot)分别检测小鼠脑干组织中各凋亡通路蛋白活化型半胱天冬酶-3(cleaved-caspase 3)、磷酸化蛋白激酶B(P-AKT)、神经胶质酸性蛋白(GFAP)、Bax、Bcl-2的表达。结果:模型组小鼠潜伏期明显高于对照组(P<0.05),黄芩苷高剂量组与模型组相比潜伏期缩短,差异显著(P<0.05),由此得出,黄芩苷最佳有效剂量为0.60 mg·kg-1。与对照组比较,模型组小鼠海马组织中MDA含量明显升高、SOD和GSH-Px活性明显降低(P<0.05);与模型组比较,黄芩苷高剂量组小鼠脑组织中SOD和GSH-Px活性明显提高、MDA含量明显降低(P<0.05)。从蛋白变化水平来看,模型组的cleaved-caspase 3、P-AKT、GFAP蛋白表达水平与对照组相比,条带明显增强,Bax/Bcl-2的比值也明显增加(P<0.05);黄芩苷组表达水平弱于模型组(P<0.05),其中黄芩苷高剂量组表达最弱,且呈一定的量效关系。结论:黄芩苷对高原性脑缺血损伤有保护作用,其作用机制可能与强的抗氧化能力及其抑制各个靶点蛋白cleaved-caspase 3、P-AKT、GFAP、Bax、Bcl-2在凋亡通路的表达有关。This study was aimed to explore the mechanism of baicalin on high altitude cerebral hypoxia-ischemia on mice and its influence on related target protein expressions. Morris water maze was used to screen 50 Kunming mice, which were randomly divided into the model group, control group, the low dose （0.05 mg＆#183;kg-1）, middle dose （0.20 mg＆#183;kg-1） and high dose （0.60 mg＆#183;kg-1） baicalin group, with 10 rats in each group. The space memory and learning ability of mice were tested. The animal cabin with low oxygen （simulating at 4 000 m altitude） was used to establish the stable high altitude cerebral hypoxia-ischemia mouse model. Changes on SOD content, GSH-PX activities and MDA content in hippocampal tissues of mice were detected. The expressions of different target proteins, including cleaved-caspase 3, P-AKT, GFAP, Bax and Bcl-2 in brain stem of mice were detected by western blot. The results showed that the latent period of the model group was obviously longer than that of the control group （P 〈 0.05）. The latent period of high dose baicalin group was shorter than the model group with significant difference （P〈 0.05）. Therefore, the best effective dose of baicalin was 0.60 mg＆#183;kg-1. Compared with the control group, the content of MDA in the hippocampal tissues of mice in the model group was significantly increased; the SOD and GSH-PX activity were obviously reduced （P 〈 0.05）. Compared with the model group, the SOD and GSH-PX activity were obviously increased in the brain tissues of mice in the high dose baicalin group; and the content of MDA was obviously reduced （P 〈 0.05）. From the level of protein changes, the stripes of cleaved-caspase 3, P-AKT, GFAP protein expressions in the model group were strengthened compared to the control group; the ratio of Bax/Bcl-2 was also obviously increased （P 〈 0.05）. The expression of the baicalin group was lower than that of the model group （P 〈 0.05）. Among them, the expression of the high dose baicalin g

关 键 词：黄芩苷 高原性脑缺血缺氧 活化型半胱天冬酶-3 磷酸化蛋白激酶B 神经胶质酸性蛋白 B细胞淋巴瘤/白血病-2 

分 类 号：R285.5[医药卫生—中药学]