人参皂苷Rg1对寡聚态Aβ_(1-42)增加p38丝裂原活化蛋白激酶活性诱导神经元损伤的可能影响  

The Possible Effect of Ginsenoside Rg1 on Oligomeric Aβ_(1-42) Increasing p38 MAPK Activity and Inducing Neuronal Injury

作　　者：何饶丽 林楠[2] 方丽君[3] 黄天文[1,2] HE Raoli;LIN Nan;FANG Lijun;HUANG Tianwen(Department of Neurology, Fujian Medical University Union Hospital, Fuzhou 350001,China;Fujian Key Laboratory of Vascular Aging, Fujian Medical University, Fuzhou 350001, China;Department of Ophthalmology, Fujian Medical University Union Hospital, Fuzhou 350001, China)

机构地区：[1]福建医科大学附属协和医院神经内科,福州350001 [2]福建省血管衰老重点实验室(福建医科大学),福州350001 [3]福建医科大学附属协和医院眼科,福州350001

出　　处：《福建医科大学学报》2022年第2期97-102,共6页Journal of Fujian Medical University

基　　金：福建省自然科学基金项目(2020J011035);福建省卫生计生科研人才培养项目(青年科研课题)(2018-1-41);福建医科大学启航基金项目(2017XQ1033)。

摘　　要：目的探讨人参皂苷Rg1对β-淀粉样蛋白1-42(Aβ_(1-42))增加皮质神经元细胞p38丝裂原活化蛋白激酶(p38 MAPK)活性、诱导神经元损伤的影响。方法采用经神经元特异性抗体检测C57BL/6胎鼠来源的皮质神经元为研究对象,运用寡聚态Aβ_(1-42)诱导神经元损伤,把神经元分为空白对照组、Aβ_(1-42)单独作用组(模型组)、SB203580处理组、人参皂苷Rg1处理组、人参皂苷Rg1单独作用组。采用Western-blot方法检测p38、磷酸化p38(p-p38)的蛋白水平,采用光学显微镜观察神经元形态,采用TUNEL染色和caspase-3活性检测神经元凋亡相关指标。结果(1)在寡聚态Aβ_(1-42)作用5和15 min时,皮质神经元中p-p38蛋白水平均较空白对照组明显升高,差别均有统计学意义(P<0.05)。(2)与模型组比较,人参皂苷Rg1处理组中,不同浓度(2.5、5.0和10.0μmol/L)的人参皂苷Rg1作用后,寡聚态Aβ_(1-42)诱导升高的p-p38/p38水平均明显回落,差别均有统计学意义(P<0.001)。与空白对照组比较,仅予以10.0μmol/L的人参皂苷Rg1也可降低皮质神经元的p-p38/p38水平,差别有统计学意义(P<0.005)。(3)在皮质神经元的形态学观察中,10.0μmol/L的人参皂苷Rg1处理组的皮质神经元突触的完整性、流畅性均较模型组明显改善;在TUNEL染色及caspase-3活性检测中,10.0μmol/L的人参皂苷Rg1处理组TUNEL阳性的凋亡神经元比例及caspase-3活性均较模型组明显降低(P<0.01)。结论p38 MAPK信号通路可能参与人参皂苷Rg1减轻寡聚态Aβ_(1-42)诱导的皮质神经元的损伤过程。Objective To investigate the effect of ginsenoside Rg1 on the increase of p38 mitogen activated protein kinase(p38 MAPK)activity and neuronal injury induced by amyloidβ-protein 1-42(Aβ_(1-42))in cortical neurons.Methods The cortical neurons of C57BL/6 fetal rats were detected by neuron specific antibody as the object of study.We used oligomeric Aβ_(1-42) to induce neuronal damage,and divided neurons into blank control group,oligomeric Aβ_(1-42) group,SB203580 treatment group,ginsenoside Rg1 treatment group and only ginsenoside Rg1 group.The protein levels of p38 and p-p38 were detected by Western-blot,and the morphology of neurons was observed by light microscope.TUNEL staining and caspase-3 activity were used to detect the related indexes of neuronal apoptosis.Results(1)Compared with the blank control group,the level of p-p38 protein in cortical neurons increased significantly in the presence of oligomeric Aβ_(1-42) on 5 min and 15 min(P<0.05);(2)Compared with the model group(oligomeric Aβ_(1-42) group),ginsenoside Rg1 at different concentrations(2.5,5.0 and 10.0μmol/L)significantly reduced the level of p-p38/p38 in the ginsenoside Rg1 treatment group(P<0.001).Compared with the blank control group,only ginsenoside Rg1 group also could reduce the level of p-p38/p38 in cortical neurons(P<0.005);(3)In the morphogenetic observation of cortical neurons,compared to the model group(oligomeric Aβ_(1-42) group),synaptic integrity and fluency significantly improved in the 10.0μmol/L ginsenoside Rg1 treatment group.And compared to the model group,the 10.0μmol/L ginsenoside Rg1 treatment group showed a decrease in the ratio of TUNEL positive apoptotic neurons to total cells and caspase-3 activity(P<0.001).Conclusion p38 MAPK signaling pathway participates in ginsenoside Rg1 to alleviate oligomeric Aβ_(1-42) induced cortical nerve damage process.

关 键 词：阿尔茨海默病 人参皂苷RG1 P38丝裂原活化蛋白激酶 

分 类 号：R28[医药卫生—中药学]