摘要
目的:探讨雌激素抑制剂作用下加味脑泰方对去势脑缺血大鼠海马ERα蛋白及ATF4/CHOP/Puma通路相关蛋白的影响。方法:将30只雌性SD大鼠随机分为假手术组、模型组、ICI组、溶剂组、ICI+雌激素组、ICI+加味脑泰方组,每组5只。除假手术组外,其余各组大鼠均制备去势模型(行双侧去卵巢术);行去卵巢术后第11天ICI+雌激素组、ICI+加味脑泰方组分别给予0.18mg/kg 17β-E2、24g/kg加味脑泰方灌胃,连续灌胃3d。在去卵巢术后第14天ICI组、ICI+雌激素组、ICI+加味脑泰方组大鼠制备脑缺血模型前10min侧脑室注射ICI182780,溶剂组给予等量的DMSO进行侧脑室注射。制备脑缺血模型后24h取海马,Western blotting检测ERα、ATF4、CHOP、Puma、Bcl-2、Bax、Caspase-3蛋白表达。结果:大鼠去双侧卵巢、造脑缺血模型后海马ATF4、CHOP、Puma、Bax、caspase-3蛋白的表达显著升高(P<0.01),ERα、Bcl-2蛋白表达显著降低(P<0.01);给予侧脑室注射ICI182780后ATF4、CHOP、caspase-3、Puma蛋白表达升高更显著(P<0.01,P<0.05),ERα蛋白表达下降更显著(P<0.01);而给予加味脑泰方干预后大鼠海马ATF4、CHOP、Puma、caspase-3蛋白表达显著下降(P<0.01),ERα、Bcl-2蛋白表达显著升高(P<0.01)。ERα蛋白表达与Bcl-2蛋白表达呈正相关(P<0.05),ERα蛋白表达与ATF4、CHOP、Puma、Bax、caspase-3蛋白表达呈负相关(P<0.01)。结论:加味脑泰方可能通过提高ERα表达而调节ATF4/CHOP/Puma通路相关蛋白的表达而抗脑缺血损伤。
Objective:To investigate the effects of Jiawei Naotai Formula on ERα protein and ATF4/CHOP/Puma pathway-related protein in hippocampus of ovariectomized rats with cerebral ischemia with the action of estrogen inhibitor.Methods:Thirty female SD rats were randomly divided into sham operation group,model group,ICI(ICI182780)group,solvent group,ICI+estrogen group and ICI+Jiawei Naotai Formula group,5 in each group.Except the sham operation group,other rats were prepared castration model(bilateral ovariectomy).On the 11th day after ovariectomy,ICI+estrogen group and ICI+Jiawei Naotai Formula group were given 0.18mg/kg 17β-E2 and 24g/kg Jiawei Naotai Formula respectively for 3 days.On the 14th day after ovariectomy,ICI 182780 was injected into the lateral ventricle of rats in ICI group,ICI+estrogen group and ICI+Jiawei Naotai Formula group 10 minutes before the establishment of cerebral ischemia model,and DMSO was injected into the lateral ventricle of rats in solvent group.The hippocampus was taken 24h after the cerebral ischemia model was prepared.The protein expressions of ERα,ATF4,CHOP,Puma,Bcl-2,Bax and caspase-3 were detected by Western blotting.Results:The protein expressions of ATF4,CHOP,Puma,Bax and caspase-3 in hippocampus were significantly increased(P<0.01)after bilateral ovariectomy and cerebral ischemia in rats,while the protein expressions of ERαand Bcl-2 were significantly decreased(P<0.01).When ICI182780 was injected into lateral ventricle,the protein expressions of ATF4,CHOP,Puma and caspase-3 were increased more significantly(P<0.01,P<0.05),and the protein expressions of ERαwere decreased more significantly(P<0.01).After the intervention of Jiawei Naotai Formula,the protein expressions of ATF4,CHOP,Puma,caspase-3 in hippocampus of rats were significantly decreased(P<0.01),and the protein expressions of ERαand Bcl-2 were significantly increased(P<0.01).ERαprotein expression was positively correlated with Bcl-2 protein expression(P<0.05),while ERαprotein expression was negatively correlated with ATF4,CHOP,Puma,Bax and caspase-3 protein expression(P<0.01).Conclusion:Jiawei Naotai Formula may prevent cerebral ischemia injury by regulating the expression of ATF4/CHOP/Puma pathway-related proteins through increasing the expression of Erα.
作者
秦莉花
王国佐
刘林
黄娟
刘洋
易亚乔
杨梅
程诚
李富周
葛金文
QIN Li-hua;WANG Guo-zuo;LIU Lin;HUANG Juan;LIU Yang;YI Ya-qiao;YANG Mei;CHENG Cheng;LI Fu-zhou;GE Jin-wen(Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-cerebral Diseases,Hunan University of Chinese Medicine,Changsha 410208,China;School of Nursing,Hunan University of Chinese Medicine,Changsha 410208,China;The First Affiliated Hospital,Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2020年第7期3594-3597,共4页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
湖南省自然科学基金项目(No.2018J J3390,No.2019JJ50434)
湖南省教育厅科学研究项目(No.17B196,N o.18C0379,No.18A206)
长沙市科技计划项目(No.kq1801045)
国家自然科学基金项目(No.81904180)。
