他莫昔芬对雌激素抗大鼠皮质神经元细胞凋亡作用的影响  

Effect of tamoxifen on neuroprotection of estrogen against apoptosis in rat cortical neurons

作　　者：周璘[1] 任慕兰[2] 

机构地区：[1]南京医科大学附属南京妇幼保健院妇产科,南京210004 [2]东南大学附属中大医院妇产科,南京210009

出　　处：《现代妇产科进展》2012年第7期544-547,共4页Progress in Obstetrics and Gynecology

摘　　要：目的:研究雌激素是否可通过调节Bcl-2及凋亡蛋白酶活化因子1(Apaf-1)的表达来抑制β淀粉样蛋白(Aβ)诱导的大鼠神经细胞凋亡,以及雌激素受体阻滞剂他莫昔芬(TMX)对雌激素效应的影响。方法:通过Hochest33258荧光染色及Annexin V/PI双染色流式细胞术观察17β-雌二醇(17β-E2)及TMX对Aβ(25-35)诱导的大脑皮质神经元细胞凋亡的影响,用半定量RT-PCR方法检测Bcl-2及Apaf-1在mRNA的表达。结果:Aβ组神经元细胞凋亡率显著高于空白对照组(P<0.01);Aβ组神经元细胞中Bcl-2 mRNA表达显著低于对照组(P<0.01),但Apaf-1 mRNA的表达显著高于对照组(P<0.01)。用1nmol/L及30nmol/L 17β-E2分别预处理后,与Aβ组相比,凋亡率显著降低(P<0.01),Bcl-2 mRNA表达显著升高(P<0.01),Apaf-1 mRNA表达显著降低(P<0.01)。用TMX分别加1nmol/L或30nmol/L 17β-E2预处理后,与单用17β-E2相比,凋亡率显著升高(P<0.05),Bcl-2 mRNA的表达显著降低(P<0.01),Apaf-1 mRNA表达显著升高(P<0.05)。TMX+Aβ组的凋亡率及Bcl-2、Apaf-1 mRNA的表达与Aβ组无显著差异(P>0.05)。结论:雌激素可通过上调Bcl-2及下调Apaf-1的表达来抑制Aβ诱导的大鼠皮质神经元细胞凋亡,雌激素受体在此效应中起重要作用。Objective：To determine whether estrogen attenuates apoptosis induced by β-amyloid protein（Aβ） in primary cultures of rat cortical neurons and whether the process mediated by modulation of the expressions of B-cell leukemia/lymphoma 2（Bcl-2） and apoptotic protease-activating factor 1（Apaf-1）.Furthermore,estrogen receptor antagonist tamoxifen（TMX） neutralized the neuroprotective effect of estrogen was explored.Methods：The effects of 17β-E2 and TMX on Aβ（25-35）-induced apoptosis in primary rat cortical neurons were observed by Hochest33258 fluorescence staining and flow cytometry detection with Annexin V/PI double-staining.The expressions of Bcl-2 and Apaf-1 mRNA were determined by semi-quantitative reverse transcription and polymerase chain reaction（RT-PCR）.Results：The apoptosis rate in Aβ group was higher than that in control group（P0.01）.The expression of Bcl-2 mRNA in Aβ group was lower than that in control group（P0.01）,and the expression of Apaf-1 mRNA in Aβ group was higher than that in control group（P0.01）.When pretreated with 1nmol/L and 30nmol/L 17β-E2,the apoptosis rate in the cells significantly decreased compared with Aβ group（P0.01）,the expression of Bcl-2 mRNA significantly increased（P0.01）and Apaf-1 mRNA significantly decreased（P0.01）.When pretreated with 1nmol/L and 30nmol/L 17β-E2 separately,at one time with TMX,the apoptosis rate significantly increased（P0.05） compared with 17β-E2＋Aβ group,the expression of Bcl-2 mRNA significantly decreased（P0.01）and Apaf-1 mRNA significantly increased（P0.05）.There were no significantly difference in the rate of apoptosis,the expressions of Bcl-2 mRNA and Apaf-1 mRNA in Aβ group compared with that in TMX＋Aβ group（P0.05）.Conclusion：Estrogen protect rat primary cortical neurons against apoptosis which induced by Aβ（25-35） through up-regulation of Bcl-2 and down-regulation of Apaf-1.Estrogen receptor play an important role on the effect.

关 键 词：雌激素 他莫昔芬 Β淀粉样蛋白 神经细胞培养 Bcl-2 APAF-1 

分 类 号：R711.75[医药卫生—妇产科学]