孕酮及别孕烯醇酮对Aβ_(25-35)诱导的神经元损伤作用的影响

Effects of progesterone and allopregnanolone treatments on Aβ_(25-35) induced neuronal toxicity

目的:研究孕酮及别孕烯醇酮对Aβ25-35诱导的神经元损伤作用的影响。方法:采用Aβ25-35(1μmol.L-1)处理原代培养的大鼠大脑皮质神经元建立损伤模型,另分别加入不同浓度孕酮及别孕烯醇酮与Aβ25-35共孵育24h,观察神经元的形态学变化并测定存活率(MTT法)。结果:与模型组比较,孕酮共孵育组神经元生存状况明显改善,神经元存活率浓度依赖性地升高(r=0.757,P<0.01),高剂量组的存活率为(100.7±7.9)%,与对照组比较无统计学差异(P>0.05);别孕烯醇酮共孵育组神经元生存状况与模型组比较无明显改善,神经元存活率呈浓度依赖性降低(r=-0.841,P<0.01)。结论:神经甾体孕酮能浓度依赖性地抑制Aβ25-35诱导的神经毒性作用,提高细胞存活率;孕酮的代谢物别孕烯醇酮不能对抗Aβ25-35引起的神经元损伤,并浓度依赖性地加重上述损伤任用。

OBJECtIVE To investigate the effects of progesterone and allopregnanolone treatments on the neurotoxicity induced by Aβ25-35 in primary rat cortical neurons. METHODS Primary cultured rat cortical neurons were treated with Aβ25-35 （ 1 μmol.L-1） to acchieve a neuron damage model. Meanwhile, progesterone and allopregnanolone were co-added with μ at 3 different concentrations respectively. Twenty-four hours after co-incubation, the morphological changes were observed under inverted microscope and the neuron viability was determined as surviving rate by MTT. RESULTS Compared with the model group, improved surviving conditions were found in progesterone co-incubation groups. The neuron viability in the progesterone groups increased in a dose-dependent manner（r = 0. 757, P-（0. 01 ）. The neuron viability in the high concentration progesterone group was （ 100. 7 ± 7. 9）%, which had no difference with the control group （P〉0. 05）. No improved surviving conditions were found in allopregnanolone co-incubation groups. The neuron viability in the allopregnanolone groups decreased in a dose-dependent manner（r = - 0. 841, P〈 0. 01）. CONCLUSION Progesterone, an active neurosteroid, inhibited the Aβ25-35 neurotoxicity and increased neuron viability in a dose-dependent way. Allopregnanolone, the metabolite of progesterone, showed no improvemeat of Aβ25-35 neurotoxicity, and aggregated its damage dose-dependently.