摘要
目的 观察外源性补充尿石素A(urolithin A,UA)是否可以通过诱导线粒体自噬缓解老年小鼠术后认知功能障碍(postoperative cognitive dysfunction,POCD)的发生.方法 将56只C57BL/6J老年雄性小鼠随机分为4组:假手术组、手术组、UA组和抑制剂组,每组14只.假手术组小鼠在腹部进行表面性切口模拟手术,手术组、UA组和抑制剂组行脾脏切除术.术后对UA组和抑制剂组静脉注射UA和UA+3-MA(线粒体自噬抑制剂).术后3天应用ELISA法测定小鼠海马组织匀浆丙二醛(malondial-dehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)水平;Western blot法测定小鼠海马组织匀浆中 PTEN 诱导假定激酶 1(PTEN-induced putative kinase 1,PINK1)和 Parkin 蛋白水平(n=6);应用水迷宫实验检测小鼠术后3天的行为认知情况(n=8).结果 手术引起老年小鼠术后3天认知功能下降(P＜0.05),海马区脑组织PINK1和Parkin蛋白水平下降(P＜0.05),氧化应激因子SOD水平水平降低,MDA水平升高(P＜0.05);与手术组比较,UA组小鼠术后认知功能显著提高(P＜0.05),海马区脑组织PINK1和Parkin蛋白水平升高(P＜0.05),氧化应激因子SOD水平水平升高,MDA水平降低(P＜0.05);而线粒体自噬抑制剂减弱了 UA对于老年小鼠术后认知功能的保护(P＜0.05).结论 UA通过激活线粒体自噬功能,抑制海马区神经元氧化应激,缓解老年小鼠术后认知功能的减退.
Abstract
Objective To observe whether exogenous supplementation of urolithin A(UA)can alleviate postoperative cognitive dysfunction(POCD)in elderly mice by inducing mitophagy.Methods Fifty-six C57BL/6J elderly male mice were randomly divided into 4 groups:sham group,operation group,UA group and inhibitor group.Splenectomy was performed in the oper-ation group,UA group and inhibitor group.UA and UA+3-MA(mitophagy inhibitor)were injected intravenously into UA group and inhibitor group after operation.Malondialdehyde(MDA)and superoxide dismutase(SOD)levels in mice hippocampus were measured by ELISA three days after operation;The levels of PTEN-induced putative kinase 1(PINK1)and parkin protein in mice hippocampus were measured by Western blot;Morris water maze test was used to detect the behavior and cognitive function of mice 3 days after operation(n=8).Results The cognitive function of the elderly mice decreased(P＜0.05),the levels of PINK1 and Par-kin protein in the hippocampus decreased(P＜0.05),and SOD level decreased and MDA lev-el increased(P＜0.05);Compared with the operation group,the cognitive function of mice in the UA group was significantly improved(P＜0.05),the levels of PINK1 and Parkin protein in the hippocampus were increased(P＜0.05),and SOD level increased and MDA level de-creased(P＜0.05);However,mitophagy inhibitors attenuated the protective effect of UA on cognitive function in elderly mice(P＜0.05).Conclusion UA can inhibit oxidative stress in hippocampal neurons by activating mitophagy and alleviate the cognitive decline in elderly mice after operation.
基金项目
黑龙江省自然科学基金优秀青年项目(YQ2019H015)
维普
万方数据