黄芩茎叶黄酮抑制冈田酸引起大鼠脑内PHF异常生成和蛋白磷酸酶的调节机制  

Flavonoids from stem and leaf of Scutellaria baicalonsis Georgi inhibit PHF abnormality and regulatory mechanism of protein phosphatase in rats' brain induced by okadaic acid

作　　者：王小青[1] 高杨[1] 董永彩[2] 商亚珍[1] WANG Xiaoqing;GAO Yang;DONG Yongcai;SHANG Yazhen(Hebei Province Key Research Office of Traditional Chinese Medicine Against Dementia, Hebei Province Key Laboratory of Traditional Chinese Medicine Research and Development, Institute of Traditional Chinese Medicine, Chengde Medical College;Workers Hospital of Chengde Iron & Steel Group Co., Ltd, Chengde 067000 , China)

机构地区：[1]河北省中医药抗痴呆重点研究室,河北省中药研究与开发重点实验室,承德医学院中药研究所 [2]承德钢铁集团有限公司总医院,河北承德067000

出　　处：《中国病理生理杂志》2018年第1期94-100,共7页Chinese Journal of Pathophysiology

基　　金：河北省首届百名优秀创新人才支持计划项目(首届);河北省教育厅科学技术重点资助项目(No.ZD20131022);河北省高等学校中药重点学科资助项目(冀教高[2013]4号);承德医学院中药药理学重点发展学科资助项目(冀医发[2014]8号)

摘　　要：目的:探讨黄芩茎叶黄酮(SSF)对冈田酸(OA)引起的大鼠脑内双螺旋细丝(PHF)异常生成的抑制作用及其对蛋白磷酸酶(PP)的调节机制。方法:雄性SD大鼠,采用侧脑室注射OA(200 ng/kg)建立记忆障碍模型,Morris水迷宫进行记忆障碍模型筛选,取造模成功大鼠每日分别灌胃25、50和100 mg/kg SSF,连续36 d。Western blot法测定大鼠皮层与海马组织中PHF、PP1、PP2A-Cα、PP2A-Cβ、PP2CA和PP2CB的蛋白表达,以银杏叶黄酮作为阳性对照药。结果:与假手术组大鼠相比,模型组大鼠皮层与海马中PHF的蛋白表达明显增加(P<0.01),皮层与海马组织中PP2A-Cα和PP2A-Cβ及海马组织中PP2CB蛋白表达明显降低(P<0.05),皮层中PP2CA和PP2CB的蛋白表达明显增加(P<0.01),皮层中PP1的蛋白表达明显降低(P<0.01)。与模型大鼠比较,灌胃25、50和100 mg/kg SSF 36 d不同程度地逆转了OA所致大鼠皮层与海马组织中PHF、PP2A-Cα和PP2ACβ及皮层中PP1的蛋白表达异常,对PP2CA和PP2CB蛋白表达无显著性影响,银杏叶黄酮也表现出与SSF相似的结果。结论:SSF能够明显抑制OA引起的大鼠脑内PHF异常生成,该作用可能与SSF调节大脑皮层和海马组织中PP1、PP2A-Cα和PP2A-Cβ的蛋白表达有关,而与调节PP2CA和PP2CB的关系较小。AIM:To investigate the effect of flavonoids from stem and leaf of Scutellaria baicalonsis Georgi(SSF)on paired helical filament(PHF)abnormality and the regulatory mechanism of protein phosphatase(PP)in rats’brain induced by okadaic acid(OA).METHODS:Male Sprague-Dawley(SD)rats were microinjected with OA(200ng/kg)by the lateral ventricle to establish a memory impairment model.Morris water maze was used to screen the memory impairment model.The successful model rats were continuous intragastric infusion(ig)SSF for36days.The relative protein expression of PHF,PP1,PP2A-Cα,PP2A-Cβ,PP2CA and PP2CB in the rat cerebral cortex and hippocampus were detected by Western blot.GinKgo biloba leaf flavonoids(GLF)were used as positive control drug.RESULTS:Compared with the sham-operated rats,the relative protein expression of PHF in the cerebral cortex and hippocampus and PP1in cortex of model rats were significantly increased(P<0.01),and the protein expression of PP2A-Cα,PP2A-Cβin the cerebral cortex and hippocampus and PP2CB in the hippocampus were decreased(P<0.05),while the relative protein expression of PP2CA and PP2CB in the cortex were significantly increased(P<0.01).SSF reversed the abnormality in the protein expression of PHF,PP2A-Cαand PP2A-Cβin rat cortex and hippocampus and PP1in rat cortex induced by OA(P<0.01),which had no significant effect on the relative protein expression of PP2CA and PP2CB.GLF also showed similar results to SSF.CONCLUSION:SSF significantly reduces the abnormal formation of PHF in rats’brain induced by OA,which may be related to the regulation of PP1,PP2A-Cαand PP2A-Cβexpression,but not with PP2CA and PP2CB expression.

关 键 词：黄芩茎叶黄酮 冈田酸 蛋白磷酸酶 双螺旋细丝 阿尔茨海默病 

分 类 号：R742[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]