补阳还五汤精简方对大脑中动脉阻塞模型大鼠海马组织Cdk5的调控  

Regulation of thin recipe of Buyang Huanwu decoction on Cdk5 expression of rats after cerebral ischemia

作　　者：刘芳[1] 王宇红[2] 邵乐[2] 夏相宜 佘颜[3] 蔡光先[2] 

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]湖南中医药大学湖南省中药粉体与创新药物省部共建国家重点实验室培育基地中药粉体关键技术及装备国家地方联合工程实验室,湖南长沙410208 [3]湖南中医药大学医学院,湖南长沙410208

出　　处：《中国药理学通报》2017年第8期1176-1181,共6页Chinese Pharmacological Bulletin

基　　金：国家重点基础研究发展计划资助项目(No2012CB723503);湖南省中医药科研计划项目(No2014135);湖南省十二五中药学重点学科资助

摘　　要：目的评价补阳还五汤精简方对大脑中动脉阻塞(MCAO)模型大鼠海马组织周期素依赖性蛋白激酶5(cyclin-dependent kinase 5,Cdk5)的调控。方法将♂SD大鼠随机分为假手术组、MCAO模型组、补阳还五汤干预组(灌胃3.15 g·kg^(-1))及补阳还五汤精简方干预组(灌胃2.41 g·kg^(-1)),每组按给药后1、3、7、14、28 d再各分5小组。采用免疫组化法、Western blot法和RT-PCR法考察不同时间点各组大鼠海马组织中Cdk5的表达。结果 MCAO模型大鼠海马组织中,脑缺血后1 d即出现Cdk5上调趋势,并随着脑缺血的加剧,Cdk5的表达继续上调,其中mRNA及蛋白水平在7~14 d达最大,28 d则出现下降趋势,与各时间点假手术组比较P<0.01,提示脑缺血损伤将激活Cdk5信号转导途径;补阳还五汤精简方干预后的3、7、14、28 d均能明显降低Cdk5的表达,与各时间点模型组比较P<0.05,且随着干预时间的延长,下调趋势越明显,干预28 d后,Cdk5的表达接近假手术组,提示补阳还五汤精简方可下调Cdk5的异常表达,与补阳还五汤原方比,两方对Cdk5的调控差异无统计学意义(P>0.05)。结论补阳还五汤精简方可能通过调控Cdk5的表达水平对脑缺血海马组织发挥保护作用。Aim To evaluate the regulation of thin recipe of Buyang Huanwu decoction on cyclin-dependent kinase 5（ Cdk5） expressions in hippocampus tissue of rats after cerebral ischemia. Methods Male SD rats were divided into sham-operation group,MCAO group,Buyang Huanwu decoction group（ ig. 3. 15 g · kg-1）and its thin recipe composition group（ ig. 2. 41 g ·kg-1）. Each group was then divided into five subgroups based on the time after administration for 1,3,7,14,28 d respectively. Cdk5 protein and mRNA levels in each group were examined by using immunohistochemistry,Western blot and real-time PCR respectively. Results The up-regulation of Cdk5 was observed in model rat hippocampus after cerebral ischemia 1 day,and kept increasing with the aggravation of ischemia injury,the peaked expression was observed after 7 ~ 14 d,while the downtrend was observed after28 days compared with the corresponding sham-operation groups（ P〈0. 01）,suggesting that the Cdk5 signal pathway would be activated by cerebral ischemic injury. The expression of Cdk5 in thin recipe of Buyang Huanwu decoction group was significantly lower than that in model group at each time point（ P〈0. 05）,and there was also more obvious down-regulation with the extend of intervene time. The regulation effects of thin recipe of Buyang Huanwu decoction was up to the best after 28 days of administration,which indicated the thin recipe was positive to the abnormal expression of Cdk5,and there was no difference between Buyang Huanwu decoction and its thin recipe treated groups（ P〈0. 05）. Conclusion The thin recipe of Buyang Huanwu decoction could exert the protective effect by regulating Cdk5 after cerebral ischemia.

关 键 词：补阳还五汤 补阳还五汤精简方 大脑中动脉阻塞模型 细胞周期素依赖性蛋白激酶5 脑缺血 海马组织 

分 类 号：R-332[医药卫生] R289.5