抑郁模型大鼠海马组织中内质网应激调控因子的表达及β-细辛醚的干预作用  

Expression of Endoplasmic Reticulum Stress-regulating Factor in Hippocampus of Depressive Rats and Intervention of β-Asarone

作　　者：金铭[1] 蔡珍珍[1] 韩俊岩[1] 顾福灵 林岩[1] 董海影[1] 宋晓明[1] 帅智峰[1] 何宝国[1] 沈云虹[1] 肖薇[1] 张晓杰[1] 

机构地区：[1]齐齐哈尔医学院,黑龙江齐齐哈尔161006

出　　处：《中国实验方剂学杂志》2017年第8期124-129,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：黑龙江省科技厅攻关项目(PC13S06)

摘　　要：目的:研究抑郁模型大鼠海马组织中内质网应激调控因子的表达及β-细辛醚的干预作用,并探讨其相关的作用机制。方法:建立慢性轻度不可预见性应激刺激(CUMS)大鼠模型,将100只大鼠随机分为5组,分别为正常组,模型组,氟西汀组(10 mg·kg-1),β-细辛醚低剂量组(25 mg·kg-1)和高剂量组(50 mg·kg-1),每组20只,从造模第8天开始每天灌胃1次给药,连续21 d。于实验的第0天和第29天进行旷场实验;采用Nissl染色法观察各组大鼠海马组织神经元尼氏体的变化;实时荧光定量PCR(Real-time PCR)技术检测各组大鼠海马组织蛋白激酶R样内质网激酶(PERK),CCAAT/增强子结合蛋白同源蛋白(CHOP),钙网蛋白(CRT)mRNA表达情况;蛋白质免疫印迹(Western blot)技术检测各组大鼠海马组织PERK,CHOP,CRT蛋白表达。结果:经28 d慢性不可预见性温和刺激后,模型组大鼠与正常组大鼠比较,水平运动和垂直运动得分明显减少(P<0.05);β-细辛醚低、高剂量组和氟西汀组大鼠与模型组比较,水平运动和垂直运动得分明显增加(P<0.05)。尼氏染色结果显示,模型组大鼠海马组织神经元细胞浆着色变浅,尼氏小体颗粒明显减少;β-细辛醚低、高剂量组大鼠海马区神经元形态相对较好,尼氏小体颗粒较模型组增多。模型组与正常组大鼠比较,PERK,CHOP,CRT mRNA表达上调(P<0.05),与模型组比较,β-细辛醚低、高剂量组和氟西汀组中PERK,CHOP,CRT mRNA表达明显下调(P<0.05)。与正常组比较,模型组大鼠PERK,CHOP,CRT蛋白表达均明显升高(P<0.05);与模型组大鼠比较,氟西汀组、β-细辛醚低、高剂量组PERK,CHOP,CRT蛋白表达明显减少(P<0.05)。结论:β-细辛醚可能是通过调节海马内质网功能发挥抗抑郁作用。Objective： To study the expression of depressive rats and the intervention effect of β-asarone. five groups： the normal control group, the model group, dose group （25 mg·kg^-1） and the high-dose group （50 of endoplasmic reticulum stress regulators in hippocampus Method： Totally 100 SD rats were randomly divided into the fluoxetine group （10 mg·kg^-1） , the β-asarone low- mg·kg^-1） , with 20 in each one. The depression model was established by CUMS. On the 8^th day after modeling, rats in fluoxetine group and β-asarone group were treated with fluoxetine or β-asarone once daily through intragastric administration for 21 days （10 mg＇kg-l-d-I for the fluoxetine group, 25 mg·kg^-1·d^-1 for the β-asarone low-dose group, 50 mg·kg^-1·d^-1 for the β-asarone high-dose group）. The open field test was carried out to assess the CUMS model and rats＇ ethological changes on the 0^th and 29^th day; The changes of nissl bodies in hippocampus neurons were observed by Nissl staining; The mRNA expressions of protein kinase R sample endoplasmic reticulum kinase （PERK）, CCAAT/EBP homologous protein （CHOP）, calprotectin （CRT） were tested by Real-time fluorescent quantitative PCR; The protein expressions of PERK, CHOP and CRT were detected by Western blot. Result： After CUMS for 28 days, scores of horizontal motion and vertical motion in model group were obviously lower than control group （P 〈 0.05） , whereas those in β-asarone low-dose group, β-asarone high-dose group, fluoxetine group were higher model group （P 〈 0.05 ）. Nissl staining results showed that the color of neurons in control group became light, with less nissl bodies; β-asarone low-dose group, β-asarone high-dose group show more normal hippocampus neurons, with more Nissl bodies than model group. Compared with the model group, mRNA expressions of PERK, CHOP and CRT were up-regulated significantly in the model group, compared with control group （P 〈 0.05 ） ; whereas those were down-regulated in β-asa

关 键 词：Β-细辛醚 抑郁 内质网应激蛋白激酶R样内质网激酶(PERK) CCAAT/增强子结合蛋白同源蛋白(CHOP) 钙网蛋白(CRT) 

分 类 号：R285.5[医药卫生—中药学]