{"title":"Effects of electroacupuncture on Sirt3/NLRP3/GSDMD signaling pathway in the substantia nigra of midbrain of rats with Parkinson's disease.","authors":"Yao Wang, Yan-Chun Wang, Jun Ma","doi":"10.13702/j.1000-0607.20230024","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To observe the effects on tyrosine hydroxylase (TH), α-synaptic nucleoprotein (α-syn), sirtuin 3 (Sirt3), NOD-like receptor 3 (NLRP3) and gasdermin-D (GSDMD) in the substantia nigra of midbrain after electroacupuncture (EA) at \"Fengfu\"(GV16), \"Taichong\" (LR3) and \"Zusanli\" (ST36) in rats of Parkinson's disease (PD), so as to explore the mechanism of EA in treatment of PD.</p><p><strong>Methods: </strong>SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The PD model was established by injecting rotenone into the neck and back, lasting 28 days. In the EA group, EA was applied to GV16, LR3 and ST36, 30 min each time, once daily, consecutively for 28 days. The open-field test was adopted to detect the total distance of autonomic movement of rats, and the pole climbing test was used to detect the body coordination ability of rats. In the substania nigra of midbrain, the positive expression of TH was determined using immunohistochemistry, the mRNA expression levels of α - syn, Sirt3, NLRP3 and GSDMD were detected by quantitative real-time fluorescence PCR, and the protein expression levels of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and cysteinyl aspartate specific proteinase (Caspase)-1 were detected by Western blot.</p><p><strong>Results: </strong>Compared with the control group, the total distance of autonomous movement was decreased (<i>P</i><0.01) in the model group, and the score of pole climbing experiment was increased (<i>P</i><0.01)；in the midbrain substantia nigra the positive expression of TH was decreased (<i>P</i><0.01)；the mRNA expression level of Sirt3 was decreased (<i>P</i><0.01), and those of α-syn, NLRP3 and GSDMD were increased (<i>P</i><0.01)；while the protein expression levels of NLRP3, ASC and Caspase-1 were increased (<i>P</i><0.01). When compared with the model group, the total distance of autonomous movement in open field experiment was increased (<i>P</i><0.01) in the EA group and the score of pole climbing experiment was lower (<i>P</i><0.05)；in the midbrain substantia nigra the positive expression of TH was increased (<i>P</i><0.01)；the mRNA expression level of Sirt3 in the midbrain substantia nigra was increased (<i>P</i><0.01), and those of α-syn, NLRP3 and GSDMD were reduced (<i>P</i><0.01)；while the protein expression levels of NLRP3, ASC and Caspase-1 decreased (<i>P</i><0.01, <i>P</i><0.05).</p><p><strong>Conclusions: </strong>EA at \"GV16\" \"LR3\" and \"ST36\" can repair the neuronal injury, clear the abnormal accumulation of α-syn in the substania nigra of midbrain, and ameliorate mitochondrial damage in PD rats, which may be obtained by regulating Sirt3/NLRP3/GSDMD signaling pathway, so as to delay the occurrence and development of Parkinson's disease.</p>","PeriodicalId":34919,"journal":{"name":"针刺研究","volume":"49 4","pages":"384-390"},"PeriodicalIF":0.0000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"针刺研究","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.13702/j.1000-0607.20230024","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: To observe the effects on tyrosine hydroxylase (TH), α-synaptic nucleoprotein (α-syn), sirtuin 3 (Sirt3), NOD-like receptor 3 (NLRP3) and gasdermin-D (GSDMD) in the substantia nigra of midbrain after electroacupuncture (EA) at "Fengfu"(GV16), "Taichong" (LR3) and "Zusanli" (ST36) in rats of Parkinson's disease (PD), so as to explore the mechanism of EA in treatment of PD.
Methods: SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The PD model was established by injecting rotenone into the neck and back, lasting 28 days. In the EA group, EA was applied to GV16, LR3 and ST36, 30 min each time, once daily, consecutively for 28 days. The open-field test was adopted to detect the total distance of autonomic movement of rats, and the pole climbing test was used to detect the body coordination ability of rats. In the substania nigra of midbrain, the positive expression of TH was determined using immunohistochemistry, the mRNA expression levels of α - syn, Sirt3, NLRP3 and GSDMD were detected by quantitative real-time fluorescence PCR, and the protein expression levels of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and cysteinyl aspartate specific proteinase (Caspase)-1 were detected by Western blot.
Results: Compared with the control group, the total distance of autonomous movement was decreased (P<0.01) in the model group, and the score of pole climbing experiment was increased (P<0.01)；in the midbrain substantia nigra the positive expression of TH was decreased (P<0.01)；the mRNA expression level of Sirt3 was decreased (P<0.01), and those of α-syn, NLRP3 and GSDMD were increased (P<0.01)；while the protein expression levels of NLRP3, ASC and Caspase-1 were increased (P<0.01). When compared with the model group, the total distance of autonomous movement in open field experiment was increased (P<0.01) in the EA group and the score of pole climbing experiment was lower (P<0.05)；in the midbrain substantia nigra the positive expression of TH was increased (P<0.01)；the mRNA expression level of Sirt3 in the midbrain substantia nigra was increased (P<0.01), and those of α-syn, NLRP3 and GSDMD were reduced (P<0.01)；while the protein expression levels of NLRP3, ASC and Caspase-1 decreased (P<0.01, P<0.05).
Conclusions: EA at "GV16" "LR3" and "ST36" can repair the neuronal injury, clear the abnormal accumulation of α-syn in the substania nigra of midbrain, and ameliorate mitochondrial damage in PD rats, which may be obtained by regulating Sirt3/NLRP3/GSDMD signaling pathway, so as to delay the occurrence and development of Parkinson's disease.
期刊介绍：
Acupuncture Research was founded in 1976. It is an acupuncture academic journal supervised by the State Administration of Traditional Chinese Medicine, co-sponsored by the Institute of Acupuncture of the China Academy of Chinese Medical Sciences and the Chinese Acupuncture Association. This journal is characterized by "basic experimental research as the main focus, taking into account clinical research and reporting". It is the only journal in my country that focuses on reporting the mechanism of action of acupuncture.
The journal has been changed to a monthly journal since 2018, published on the 25th of each month, and printed in full color. The manuscript acceptance rate is about 10%, and provincial and above funded projects account for about 80% of the total published papers, reflecting the latest scientific research results in the acupuncture field and has a high academic level. Main columns: mechanism discussion, clinical research, acupuncture anesthesia, meridians and acupoints, theoretical discussion, ideas and methods, literature research, etc.
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