尿石素A通过诱导线粒体自噬缓解老年小鼠术后认知功能减退  

Urolithin A alleviated postoperative cognitive decline in elderly mice by inducing mitophagy

作　　者：冯宝 邓希锦[2] 吴培[3] 萨那斯日古楞 FENG Bao;DENG Xi-jin;WU Pei;SANA Siriguleng(Department of Anesthesiology,Harbin The First Hospital,Harbin 150001,China;Department of Anesthesiology,The Second Affiliated Hospital of Harbin Medical University,Harbin 150081,China;Department of Neurosurgery,The First Afiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨市第一医院麻醉科,黑龙江哈尔滨150001 [2]哈尔滨医科大学附属第二医院麻醉科,黑龙江哈尔滨150081 [3]哈尔滨医科大学附属第一医院神经外科,黑龙江哈尔滨150001

出　　处：《哈尔滨医科大学学报》2024年第3期232-236,共5页Journal of Harbin Medical University

基　　金：黑龙江省自然科学基金优秀青年项目(YQ2019H015)。

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(malondialdehyde,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。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 operation 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 Parkin protein in the hippocampus decreased(P<0.05),and SOD level decreased and MDA level 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 decreased(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.

关 键 词：尿石素A 术后认知功能障碍 线粒体自噬 

分 类 号：R743.3[医药卫生—神经病学与精神病学]