Klotho蛋白抑制POCD老年大鼠脑组织及小胶质细胞中FGF23/NF-κB p65的表达

doi:10.13418/j.issn.1001-165x.2022.5.09

中国临床解剖学杂志 ›› 2022, Vol. 40 ›› Issue (5): 548-554.doi: 10.13418/j.issn.1001-165x.2022.5.09

Klotho蛋白抑制POCD老年大鼠脑组织及小胶质细胞中FGF23/NF-κB p65的表达

段海霞¹，王翀鹤²，王庆辉¹，姜万维¹*，黄学洙²*

1.大连大学附属中山医院麻醉科，辽宁大连 116001； 2.延边大学附属医院麻醉科，吉林延吉 133002

收稿日期:2022-06-07 出版日期:2022-09-25 发布日期:2022-10-11
通讯作者: 姜万维，硕士，主任医师，E-mail：13604941935@163.com；黄学洙，博士，副教授，E-mail：huangxuezhu72@163.com
作者简介:段海霞（1979-），女，主治医师，研究方向：老年麻醉，E-mail：duanhaixiahappy@sina.com
基金资助:
国家自然科学基金资助项目（NO.81860211）

Klotho protein inhibits FGF23/NF-κB p65 expression in aged rats and microglia of POCD

Duan Haixia¹, Wang Chonghe², Wang Qinghui¹, Jiang Wanwei¹*, Huang Xuezhu²*

1.Department of Anesthesiology, Zhongshan Affiliated Hospital of Dalian University, Dalian 116001, Liaoning Province, China; 2. Department of Anesthesiology, Affiliated Hospital of Yanbian University, Yanji 133002, Jilin Province, China

Received:2022-06-07 Online:2022-09-25 Published:2022-10-11

摘要/Abstract

摘要： 目的以POCD老年大鼠及BV2小胶质细胞作为研究对象，探究Klotho蛋白对POCD的治疗作用及机制。方法 SD老年大鼠45只，随机分为control组，七氟醚麻醉组（sevo组）、七氟醚麻醉手术组（sevo+surgery组）。采用水迷宫评估大鼠认知状态，HE、TUNEL染色和ELISA检测大鼠海马组织病变、凋亡及促炎介质的表达水平。Western blot检测大鼠海马组织和BV2细胞中相关蛋白表达。细胞免疫荧光检测BV2细胞中NF-κB p-P65表达。结果 sevo组和sevo+surgery组老年大鼠出现明显认知障碍，海马区受损，炎症因子表达增加，大量神经元细胞凋亡，Klotho蛋白表达下调，而FGF23/NF-κB通路蛋白表达上调。LPS和七氟醚诱导BV2细胞炎症因子表达增加，FGF23/NF-κB通路蛋白表达上调，然而Klotho治疗降低了上述蛋白和炎症因子的表达。结论 Klotho可能在POCD的防治中成为新的靶点，其机制可能与Klotho蛋白抑制小胶质细胞中FGF23/NF-κB的表达有关。

关键词: 七氟醚； , , 术后认知功能障碍； , , 克老素； , , 小胶质细胞； , , 成纤维细胞生长因子23； , , 核因子-κB

Abstract: Objective To explore the therapeutic effect and mechanism of Klotho protein on POCD by selecting the POCD aged rats and BV2 microglia as research objects. Methods Forty-five SD aged rats were divided into a control group, a sevo group and a sevo+surgery group, randomly. The rats cognitive status were assessed by water maze. HE staining, TUNEL staining and ELISA were used to detect the pathological changes, apoptosis and expression levels of inflammatory factors in rat hippocampus. Western blot was used to detect the related proteins expression of the rat hippocampal tissue and BV2 cells. Cell immunofluorescence was used to detect the NF-κB p65 expression in BV2 cells. Results Aged rats in the sevo and sevo+surgery groups showed significant cognitive impairment, hippocampal region damage, increased expression of inflammatory factors, apoptosis of a large number of neuronal cells, down-regulation of Klotho protein expression, and up-regulation of FGF23/NF-κB pathway protein expression. LPS and sevoflurane induced increased expression of inflammatory factors and up-regulated expression of FGF23/NF-κB pathway protein in BV2 cells, while treatment with Klotho decreased the expression levels of inflammatory factors and the above proteins. Conclusions Klotho may become a new target in the prevention and treatment of POCD, and its mechanism may be related to the inhibition of FGF23/NF-κB expression in microglia by Klotho peotein.

Key words: Sevoflurane; , Postoperative cognitive dysfunction; , Klotho; , Microglia; , FGF23; , NF-κB

中图分类号:

R614.21
Q421

段海霞, 王翀鹤, 王庆辉, 姜万维, 黄学洙. Klotho蛋白抑制POCD老年大鼠脑组织及小胶质细胞中FGF23/NF-κB p65的表达[J]. 中国临床解剖学杂志, 2022, 40(5): 548-554.

Duan Haixia, Wang Chonghe, Wang Qinghui, Jiang Wanwei, Huang Xuezhu. Klotho protein inhibits FGF23/NF-κB p65 expression in aged rats and microglia of POCD [J]. Chinese Journal of Clinical Anatomy, 2022, 40(5): 548-554.

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Klotho蛋白抑制POCD老年大鼠脑组织及小胶质细胞中FGF23/NF-κB p65的表达

Klotho protein inhibits FGF23/NF-κB p65 expression in aged rats and microglia of POCD

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