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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 study whether estrogen can inhibit Aβ-induced neuronal apoptosis by regulating the expression of Bcl-2 and Apaf-1, and whether estrogen receptor resistance Effect of Antagonist Tamoxifen (TMX) on Estrogen Effect. Methods: The effect of 17β-estradiol (17β-E2) and TMX on Aβ (25-35) -induced cerebral cortical neuron apoptosis was observed by Hochest33258 staining and Annexin V / PI double staining. Semi-quantitative RT-PCR was used to detect the mRNA expression of Bcl-2 and Apaf-1. Results: The apoptosis rate of neurons in Aβ group was significantly higher than that in blank control group (P <0.01). The expression of Bcl-2 mRNA in Aβ group was significantly lower than that in control group (P <0.01), but Apaf-1 mRNA The expression was significantly higher than that of the control group (P <0.01). After pretreatment with 1 nmol / L and 30 nmol / L 17β-E2, the apoptosis rate was significantly decreased (P <0.01) and the expression of Bcl-2 mRNA was significantly increased compared with Aβ group (P <0.01) mRNA expression was significantly lower (P <0.01). Compared with 17β-E2 alone, the apoptotic rate was significantly increased (P <0.05) and the expression of Bcl-2 mRNA was significantly decreased after pretreatment with 1 nmol / L or 30 nmol / L 17β- 0.01), Apaf-1 mRNA expression was significantly increased (P <0.05). There was no significant difference in apoptosis rate and expression of Bcl-2, Apaf-1 mRNA between TMX + Aβ group and Aβ group (P> 0.05). Conclusion: Estrogen can inhibit Aβ-induced apoptosis of rat cortical neurons by up-regulating the expression of Bcl-2 and down-regulating Apaf-1, and estrogen receptor plays an important role in this effect.