首页|经皮穴位电刺激通过PGC-1α介导的线粒体生物生成和抗氧化应激改善血管性痴呆大鼠的认知功能

经皮穴位电刺激通过PGC-1α介导的线粒体生物生成和抗氧化应激改善血管性痴呆大鼠的认知功能

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目的 探讨经皮穴位电刺激(transcutaneous electrical acupoint stimulation,TEAS)对血管性痴呆(vascular dementia,VD)大鼠认知功能的影响及其机制。方法 采用改良的双血管闭塞(2-VO)法建立VD大鼠模型。造模后分别采用TEAS和电针(EA)刺激大鼠百会穴和足三里穴,连续刺激14 d。治疗后,采用新物体识别实验、Morris水迷宫实验、Y迷宫实验评估大鼠空间记忆和学习能力。苏木精-伊红染色观察海马神经元形态;透射电镜观察海马线粒体超微结构;采用酶联免疫吸附测定试剂盒检测大鼠血清中SOD、CAT、GSH-Px、MDA和ROS水平。采用蛋白质免疫印迹法(Western blot)检测各组大鼠海马组织中PGC-1α、TFAM、HO-1、NQO1蛋白及细胞质中Keap1蛋白及细胞核中Nrf2、NRF1蛋白的表达。结果 治疗14d后,与模型组比较,VD组大鼠逃避潜伏期缩短,辨别指数、穿越原平台区域次数、原平台所在象限停留时间、交替百分比增加;TEAS可改善VD大鼠海马神经元及线粒体结构,病理染色结果显示神经元排列更规则、分布更均匀,核膜、核仁更清晰,线粒体肿胀减轻,线粒体基质密度增加,线粒体嵴更明显。血清中SOD、GSH-Px和CAT水平显著升高,MDA和ROS浓度降低。TEAS还上调了海马区PGC-1α、TFAM、NQO1、HO-1蛋白和核内NRF2、NRF1蛋白的表达水平,但下调了胞浆中Keap1蛋白的表达。结论 TEAS可改善VD大鼠的认知功能,改善海马神经元和线粒体结构,且效果优于电针,其机制可能是激活PGC-1α介导的线粒体生物发生和抗氧化应激,这也为VD的治疗提供了潜在的治疗技术和实验依据。
Transcutaneous Electrical Acupoint Stimulation Promotes PGC-1α Mediated Mitochondrial Biogenesis and Antioxidant Stress to Protect Cognitive Function in Vascular Dementia Rats
Objective The purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation(TEAS)on cognitive function of vascular dementia(VD)rats and its mechanism.Methods VD rat model was established by modified two-vessel occlusion(2-VO).After modeling,TEAS and electroacupuncture(EA)were used to stimulate Baihui and Zusanli points of rats respectively for 14 d.After treatment,novel object recognition test,Morris water maze test,and Y maze test were used to evaluate the spatial memory and learning ability of rats.Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons.Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria.Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD,CAT,GSH-Px,MDA and ROS in serum of rats.Western blot was used to detect the expression of PGC-1α,TFAM,HO-1,NQO1 proteins in the hippocampus,Keapl protein in the cytoplasm and Nrf2,NRF1 proteins in the nucleus.Results After treatment for 14 d,compared to the model group,the escape latency of VD rats decreased,while the discrimination index,the times of rats crossing the original platform area,the residence time in the original platform quadrant,and the percentage of alternation increased.TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats,showing that neurons were arranged more regularly and distributed more evenly,nuclear membrane and nucleoli were clearer,and mitochondrial swelling were reduced,mitochondrial matrix density were increased,and mitochondrial cristae were more obvious.The levels of SOD,GSH-Px and CAT in serum increased significantly,while the concentration of MDA and ROS decreased.TEAS also up-regulated the expression levels of PGC-lα TFAM,NQO1 and HO-1 proteins in the hippocampus and Nrf2,NRF1 proteins in the nucleus,but down-regulated the Keap1 protein in the cytoplasm.Conclusion TEAS can improve cognition,hippocampal neurons and mitochondrial structure of VD rats,and the effect is better than EA.The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress,which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

vascular dementiatranscutaneous electrical acupoint stimulationcognition functionPGC-1αanti-oxidantmitochondrial

康吉良、胡可、卢俊樾、胡紫薇、徐彪平、黎小毛、周俊杰、金煜、唐敏、徐蓉、温优良

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赣南医学院康复学院,赣州 341000

南京大学医学院附属鼓楼医院康复医学科,南京 210008

赣南医学院中西医结合研究中心,赣州 341000

赣南医学院心脑血管病防治教育部重点实验室,赣州 341000

赣州市康复医学重点实验室,赣州 341000

宁波市康复医院神经康复科,宁波 315040

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血管性痴呆 经皮穴位电刺激 认知功能 PGC-1α 抗氧化 线粒体

宁波市重点研发计划

2023Z173

2024

生物化学与生物物理进展
中国科学院生物物理研究所,中国生物物理学会

生物化学与生物物理进展

CSTPCD北大核心
影响因子:0.476
ISSN:1000-3282
年,卷(期):2024.51(5)
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