冬凌草甲素对脑小血管病大鼠认知功能及PERK/CHOP信号通路的影响  

Effects of Oridonin on Cognitive Function and PERK/CHOP Signaling Pathway in Rats with Cerebral Small Vessel Disease

作　　者：石磊[1] 陈宁宁[1] 郭亚培[1] 胡静伟 王新华[1] Shi Lei;Chen Ningning;Guo Yapei;Hu Jingwei;Wang Xinhua(Third Department of Neurology,Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Interventional Catheterization Room,Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第五附属医院神经内三科,郑州450052 [2]郑州大学第五附属医院介入导管室,郑州450052

出　　处：《中国药师》2022年第6期949-954,980,共7页China Pharmacist

基　　金：河南省医学科技攻关计划项目(编号:2018020240)。

摘　　要：目的:探究冬凌草甲素对脑小血管病(CSVD)大鼠认知功能及蛋白激酶R样内质网激酶(PERK)/C/EBP同源蛋白(CHOP)信号通路的影响。方法:通过体外注入同种系微栓子建立CSVD模型,将72只SD大鼠随机分为6组:假手术组、模型组、尼莫地平组(10 mg·kg^(-1))、冬凌草甲素低(5 mg·kg^(-1))、中(10 mg·kg^(-1))、高(15 mg·kg^(-1))剂量组,每组12只,除假手术组外,其余组大鼠均建模。按分组治疗28 d后,采用Morris水迷宫实验测定大鼠认知功能,试剂盒测定海马组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量,苏木精-伊红染色法(HE)观察大鼠大脑海马组织的病理学特征,逆转录-合酶链反应法(RT-PCR)测定海马组织中PERK、转录因子4(ATF4)、CHOP mRNA的表达,蛋白免疫印迹(Western blot)检测海马组织中p-PERK、PERK、ATF4、CHOP蛋白的表达。结果:与假手术组相比,模型组大鼠逃避潜伏期时间延长、跨越原平台次数减少、在目标象限停留时间缩短、海马组织SOD含量显著降低、MDA含量增加(P<0.05),海马组织产生损伤,海马组织中PERK、ATF4、CHOP mRNA及p-PERK/PERK、ATF4、CHOP蛋白表达水平显著上调(P<0.05);与模型组相比,冬凌草甲素各剂量组大鼠逃避潜伏期时间缩短、跨越原平台次数增加、在目标象限停留时间延长、海马组织SOD含量显著增加、MDA含量降低(P<0.05),海马组织病变减轻,海马组织中PERK、ATF4、CHOP mRNA及p-PERK/PERK、ATF4、CHOP蛋白表达水平下调(P<0.05),且呈剂量依赖性(P<0.05);冬凌草甲素高剂量组与尼莫地平组各项指标比较差异无统计学意义(P>0.05)。结论:冬凌草甲素可提高CSVD大鼠的认知功能,缓解大鼠CSVD症状,可能与其调控PERK/CHOP通路有关。Objective:To explore the effects of oridonin on cognitive function and protein kinase R-like endoplasmic reticulum kinase(PERK)/C/EBP homologous protein(CHOP)signaling pathway in rats with cerebral small vessel disease(CSVD).Methods:The cerebral small vessel disease model was established by injecting microemboli of the same species in vitro.Totally 72 SD rats were randomly divided into six groups:sham operation group,model group,nimodipine group(10 mg·kg^(-1)),oridonin low(5 mg·kg^(-1)),medium(10 mg·kg^(-1))and high(15 mg·kg^(-1))dose groups with 12 per group.Except the sham operation group,the other groups were modeled.After 28 days of treatment,Morris water maze test was used to measure the cognitive function of rats,the kits were used to determine the contents of superoxide dismutase(SOD)and malondialdehyde(MDA)in hippocampal tissue,hematoxylin-eosin staining(HE)was used to observe the pathological characteristics of rat brain hippocampus,reverse transcription-synthase chain reaction(RT-PCR)was used to determine the expression of PERK,transcription factor 4(ATF4)and CHOP mRNA in hippocampus,and Western blot was used to detect the expression of p-PERK,PERK,ATF4,and CHOP proteins in hippocampus.Results:Compared with those in the sham operation group,the escape latency was extended in the model group,the number of crossing the original platform was reduced,the target quadrant staying time was shortened,the SOD content in hippocampus was significantly reduced,the MDA content was increased(P<0.05),the hippocampal tissue was damaged,and the expression levels of PERK,ATF4,CHOP mRNA and p-PERK/PERK,ATF4,CHOP protein in hippocampus tissue were significantly up-regulated(P<0.05);compared with those in the model group,the escape latency was shortened in oridonin groups,the number of crossing the original platform was increased,the target quadrant staying time was extended,the SOD content in hippocampus was significantly increased,the MDA content was reduced(P<0.05),the hippocampal tissue lesions were alleviated,and t

关 键 词：冬凌草甲素 脑小血管病 认知功能 蛋白激酶R样内质网激酶/C/EBP同源蛋白信号通路 内质网应激 

分 类 号：R965.1[医药卫生—药理学]