晚期糖化终末产物对大鼠海马神经元的损伤作用与机制

Impairment effect and mechanism of advanced glycation end products on hippocampi rats

目的研究晚期糖化终末产物(AGEs)对海马神经元存活、生长的影响和机制,以探讨AGEs在阿尔茨海默病发生中的作用。方法取培养1 d的新生大鼠海马神经元,分为对照组和AGEs-BSA组。在含终浓度为100 mg.L-1、500 mg.L-1、2000 mg.L-1的牛血清白蛋白(BSA)或AGEs-BSA的培养液中培养24 h,显微镜下观察神经元形态变化,噻唑蓝(MTT)法测定神经元存活率,硫代巴比妥法测定神经元脂质过氧化物(LPO)含量。结果100 mg.L-1BSA或AGEs-BSA条件下,2组海马神经元的形态、存活率及LPO含量均无明显差异(P>0.05)。500 mg.L-1和2 000 mg.L-1条件下,AGEs-BSA组的海马神经元生长状况均较差,细胞存活率均降低(P<0.05,P<0.01),LPO含量均升高(P<0.05,P<0.01),且2 000 mg.L-1组上述变化更显著(P<0.01)。结论AGEs对体外培养的海马神经元有剂量依赖性损伤作用。过氧化应激是AGEs损伤海马神经元的途径之一。

Objective To study the effects of advanced glycation end products （AGEs） on hippoeampi neurons of new bern rats cultured in vitro,to reveal the roles of AGEs in the pathogenesis of Alzheimer＇s disease（AD）. Methods Hippoeampi cells from new-bern rats was cultured for one day and divided into control group and AGEs-BSA group. The morphologic changes of the hippocampi neurons cultured for 24 h in BSA- or AGEs-BSA-containing medium with serial concentrations （ 100mg·L^-1, 500 mg·L^-1 ,2 000 mg·L^-1 ） were observed with microscope,the survival ratioes of the neurons detected with MTT,and the contents of LPO assayed with the method of thiobarbiturate sodium. Results There were no significant difference in morphology,cell survival ratioes and LPO content between the control group（ 100mg·L^-1 concentration） and the AGEs-BSA group（ 100mg·L^-1 concentration）. Compared with the control group, the neurons grown badly in both 500 mg·L^-1 and 2 000 mg·L^-1 AGEs-BSA- containing medium, the survival ratioes decreased （ P 〈 0. 05, P 〈 0.01 ）, and the contents of LPO increased （ P 〈 0. 05, P 〈0.01 ）, all the above more significantly in the later concentration （ P 〈0.01 ）. Conclusion AGEs-BSA has dose-dependent neurotoxic effects on hippocampi neurons in vitro. Peroxidation stress is a pathway of the neurotoxic effects on hippocampi neurons.