首页|CREB磷酸化介导半枝莲黄酮改善BI-D1870所致大鼠记忆障碍

CREB磷酸化介导半枝莲黄酮改善BI-D1870所致大鼠记忆障碍

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目的:探讨半枝莲黄酮(SBFs)通过促进CREB磷酸化改善BI-D1870所致大鼠记忆障碍。方法:腹腔注射BI-D1870建立大鼠记忆障碍模型，Morris水迷宫筛选记忆障碍成功模型，模型成功大鼠随机分为模型组、SBFs组和CREB磷酸化激活剂Rolipram组，SBFs组大鼠灌胃140 mg·kg-1 SBFs，Rolipram组大鼠腹腔注射0。5 mg·kg-1Rolipram。Morris水迷宫检测大鼠学习记忆能力;苏木精-伊红(HE)染色观察海马皮层神经元形态;免疫组化(IHC)检测海马回与神经再生相关蛋白DCX表达;免疫荧光(IF)检测海马和皮层p-CREB-Ser142蛋白表达;实时荧光定量(qPCR)检测海马和皮层BDNF、TrkB和CREB的mRNA表达;Western blot检测海马和皮层BDNF、TrkB和p-CREB-Ser133蛋白表达。结果:腹腔注射BI-D1870可引起大鼠学习记忆障碍，神经病理学改变，海马回DCX蛋白表达降低，海马和皮层p-CREB-Ser142蛋白表达增加，BDNF、TrkB和CREB的mRNA及蛋白表达皆降低。SBFs可逆转BI-D1870所致大鼠上述异常改变，作用与Rolipram相平行。结论:SBFs与Rolipram作用相一致，能够改善BI-D1870所致的记忆障碍，其作用机制与其影响CREB磷酸化有关。
Scutellaria barbata flavonoids promote rats'memory impairment induced by BI-D1870 via CREB phosphorylation
OBJECTIVE To investigate the effects of Scutellaria barbata flavonoids(SBFs)on rats'memory impairment induced by BI-D1870 and its molecular mechanism.METHODS The memory impairment model of rats was established by intra-peritoneal injection of BI-D1870.The successful memory impairment model of rats was screened with Morris water maze.The successful model rats were randomly divided into model group,SBFs group and Rolipram group.The rats in SBFs group were orally given SBFs 140 mg·kg-1,and the rats in Rolipram group were intraperitoneally injected Rolipram 0.5 mg·kg-1.Morris water maze was used to detect the learning and memory ability of rats.Hematoxylin-eosin(HE)staining was used to observe the morphology of neurons in hippocampus and cortex of rats.Immunohistochemistry(IHC)was used to detect the protein expression of neurogenesis related protein DCX,and immunofluorescence(IF)was applied to assaying the protein expression of p-CREB-Ser142.The mRNA expression of BDNF,TrkB and CREB was assayed by real-time quantitative PCR(qPCR).The expres-sion of BDNF,TrkB and CREB proteins was measured by Western blot.RESULTS Intraperitoneal injection of BI-D1870 can cause learning and memory impairment,and neuropathological changes,also increase the hippocampal and cerebral cortex p-CREB-Ser142 protein expression,reduce the hippocampal gyrus DCX protein,and reduce BDNF,TrkB,CREB mRNA and protein expression.SBFs could dramatically regulate the above abnormal changes in the rats treated with intraperitoneal injection of BI-D1870,which was similar to the effects of Rolipram.CONCLUSION SBFs have the same effects as Rolipram in improv-ing the memory impairment induced by BI-D1870,and its mechanism is related to its influence on the CREB phosphorylation.

Scutellaria barbata flavonoidsBI-D1870CREB phosphorylationmemory disorder

张超洁、马帅、李佳慧、商亚珍

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承德医学院中药研究所/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/河北省神经损伤与修复重点实验室,河北承德 067000

半枝莲黄酮 BI-D1870 CREB磷酸化 记忆障碍

河北省自然基金资助项目河北省中医药管理局资助项目河北省中医药管理局资助项目河北省教育厅重点项目河北省教育厅重点项目河北省中医药中药药理重点学科建设项目承德医学院科技创新团队项目

H2019406063050272014062ZD20131022ZD2019057冀中医药函[2021]12号[2020]50

2024

10.13286/j.1001-5213.2024.05.06

中国医院药学杂志
中国药学会

中国医院药学杂志

CSTPCD北大核心
影响因子：1.198
ISSN：1001-5213
年,卷(期)：2024.44(5)
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