{"title":"电针通过 Sirtuin-1 通路抑制凋亡改善脑缺血再灌注损伤","authors":"Ya-Nan Luo, Rong-Hua Xu, Zhi-Tao Feng, Song-bai Yang, Ya-Guang Huang, Zhi-Gang Mei","doi":"10.4103/wjtcm.wjtcm_77_24","DOIUrl":null,"url":null,"abstract":"\n \n \n NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis is pivotal in the pathological development of cerebral ischemia/reperfusion injury (CIRI). Although previous research has shown that electroacupuncture (EA) can alleviate CIRI through sirtuin-1 (SIRT1), the mechanism has not been well elucidated. Our study aimed to clarify whether the neuroprotective functions of EA are related to the reduction in NLRP3-mediated pyroptosis through the SIRT1 pathway.\n \n \n \n Rats received daily pretreatment with EA for 5 consecutive days before undergoing middle cerebral artery occlusion surgery. The Longa score was used to assess neurologic function. Infarct volume and morphological alterations were analyzed using 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining. In addition, neuronal pyroptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling/caspase-1 and neuronal nuclear antigen/caspase-1 immunofluorescence double staining. Levels of expression of pyroptosis markers were assessed by Western blotting and enzyme-linked immunosorbent assay.\n \n \n \n EA improved deficits in neurologic function and minimized cerebral infarct volume. Mechanistically, a number of neuronal pyroptotic cells and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, and gasdermin D in the cerebral cortex were markedly reduced by EA treatment, and conversely, SIRT1 levels were increased. Notably, the specific SIRT1 inhibitor, EX527, reversed the effects of EA.\n \n \n \n EA potentially exerts a neuroprotective effect against CIRI through the SIRT1 pathway in NLRP3-mediated pyroptosis.\n","PeriodicalId":23692,"journal":{"name":"World Journal of Traditional Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Electroacupuncture Ameliorates Cerebral Ischemia-reperfusion Injury by Inhibiting Pyroptosis through the Sirtuin-1 Pathway\",\"authors\":\"Ya-Nan Luo, Rong-Hua Xu, Zhi-Tao Feng, Song-bai Yang, Ya-Guang Huang, Zhi-Gang Mei\",\"doi\":\"10.4103/wjtcm.wjtcm_77_24\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\\n \\n \\n NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis is pivotal in the pathological development of cerebral ischemia/reperfusion injury (CIRI). Although previous research has shown that electroacupuncture (EA) can alleviate CIRI through sirtuin-1 (SIRT1), the mechanism has not been well elucidated. Our study aimed to clarify whether the neuroprotective functions of EA are related to the reduction in NLRP3-mediated pyroptosis through the SIRT1 pathway.\\n \\n \\n \\n Rats received daily pretreatment with EA for 5 consecutive days before undergoing middle cerebral artery occlusion surgery. The Longa score was used to assess neurologic function. Infarct volume and morphological alterations were analyzed using 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining. In addition, neuronal pyroptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling/caspase-1 and neuronal nuclear antigen/caspase-1 immunofluorescence double staining. Levels of expression of pyroptosis markers were assessed by Western blotting and enzyme-linked immunosorbent assay.\\n \\n \\n \\n EA improved deficits in neurologic function and minimized cerebral infarct volume. Mechanistically, a number of neuronal pyroptotic cells and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, and gasdermin D in the cerebral cortex were markedly reduced by EA treatment, and conversely, SIRT1 levels were increased. 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引用次数: 0
摘要
NOD样受体蛋白3(NLRP3)介导的热蛋白沉积是脑缺血再灌注损伤(CIRI)病理发展的关键。尽管之前的研究表明电针(EA)可以通过sirtuin-1(SIRT1)缓解CIRI,但其机制尚未得到很好的阐明。我们的研究旨在阐明 EA 的神经保护功能是否与通过 SIRT1 途径减少 NLRP3 介导的热蛋白沉积有关。 大鼠在接受大脑中动脉闭塞手术前连续5天每天接受EA预处理。Longa 评分用于评估神经功能。用2,3,5-三苯基氯化四氮唑和苏木精及伊红染色分析梗死体积和形态学改变。此外,通过末端脱氧核苷酸转移酶介导的dUTP-生物素缺口端标记/caspase-1和神经元核抗原/caspase-1免疫荧光双重染色,确定了神经元的脓毒症。通过 Western 印迹法和酶联免疫吸附试验评估了热蛋白沉积标记物的表达水平。 EA改善了神经功能缺损,最大程度地缩小了脑梗塞体积。从机理上讲,EA治疗后大脑皮层中神经元凋亡细胞的数量和NLRP3、含有CARD的凋亡相关斑点样蛋白和gasdermin D的蛋白水平明显降低,相反,SIRT1的水平升高。值得注意的是,特异性 SIRT1 抑制剂 EX527 逆转了 EA 的作用。 EA可能通过SIRT1途径在NLRP3介导的热蛋白沉积过程中对CIRI发挥神经保护作用。
Electroacupuncture Ameliorates Cerebral Ischemia-reperfusion Injury by Inhibiting Pyroptosis through the Sirtuin-1 Pathway
NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis is pivotal in the pathological development of cerebral ischemia/reperfusion injury (CIRI). Although previous research has shown that electroacupuncture (EA) can alleviate CIRI through sirtuin-1 (SIRT1), the mechanism has not been well elucidated. Our study aimed to clarify whether the neuroprotective functions of EA are related to the reduction in NLRP3-mediated pyroptosis through the SIRT1 pathway.
Rats received daily pretreatment with EA for 5 consecutive days before undergoing middle cerebral artery occlusion surgery. The Longa score was used to assess neurologic function. Infarct volume and morphological alterations were analyzed using 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining. In addition, neuronal pyroptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling/caspase-1 and neuronal nuclear antigen/caspase-1 immunofluorescence double staining. Levels of expression of pyroptosis markers were assessed by Western blotting and enzyme-linked immunosorbent assay.
EA improved deficits in neurologic function and minimized cerebral infarct volume. Mechanistically, a number of neuronal pyroptotic cells and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, and gasdermin D in the cerebral cortex were markedly reduced by EA treatment, and conversely, SIRT1 levels were increased. Notably, the specific SIRT1 inhibitor, EX527, reversed the effects of EA.
EA potentially exerts a neuroprotective effect against CIRI through the SIRT1 pathway in NLRP3-mediated pyroptosis.