Electroacupuncture reduces the expression of Hba-a1 and Hbb-bt and alleviates cell apoptosis after spinal cord injury by regulating the PPARγ-CD36 signaling pathway

Li Mingjiao; Tang Chenglin; Yang Zhuxin; Zhao Hongdi; Wang Jiapei; Xing Kehan; Huang Siqin

doi:10.13406/j.cnki.cyxb.003784

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Electroacupuncture reduces the expression of Hba-a1 and Hbb-bt and alleviates cell apoptosis after spinal cord injury by regulating the PPARγ-CD36 signaling pathway

Basic research | 更新时间：2025-10-22

- Electroacupuncture reduces the expression of Hba-a1 and Hbb-bt and alleviates cell apoptosis after spinal cord injury by regulating the PPARγ-CD36 signaling pathway
- Journal of Chongqing Medical University Vol. 50, Issue 3, Pages: 311-321(2025)
- 作者机构：
  
  重庆医科大学中医药学院中医防治代谢性疾病重庆市重点实验室，重庆 400016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003784
  CLC： R651.2
- Received：22 January 2024，
  
  Revised：2024-03-11，
  
  Accepted：22 May 2024，
  
  Published：28 March 2025
- 稿件说明：
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李明娇,唐成林,杨祝歆,等.电针调控PPARγ-CD36信号通路降低Hba-a1、Hbb-bt表达减轻脊髓损伤后细胞凋亡的研究[J].重庆医科大学学报,2025,50(3):311-321.

Li Mingjiao,Tang Chenglin,Yang Zhuxin,et al.Electroacupuncture reduces the expression of Hba-a1 and Hbb-bt and alleviates cell apoptosis after spinal cord injury by regulating the PPARγ-CD36 signaling pathway[J].Journal of Chongqing Medical University,2025,50(3):311-321.
李明娇,唐成林,杨祝歆,等.电针调控PPARγ-CD36信号通路降低Hba-a1、Hbb-bt表达减轻脊髓损伤后细胞凋亡的研究[J].重庆医科大学学报,2025,50(3):311-321. DOI： 10.13406/j.cnki.cyxb.003784.

Li Mingjiao,Tang Chenglin,Yang Zhuxin,et al.Electroacupuncture reduces the expression of Hba-a1 and Hbb-bt and alleviates cell apoptosis after spinal cord injury by regulating the PPARγ-CD36 signaling pathway[J].Journal of Chongqing Medical University,2025,50(3):311-321. DOI： 10.13406/j.cnki.cyxb.003784.

摘要

目的

本研究旨在建立脊髓损伤小鼠模型探讨电针（electroacupuncture，EA）干预小鼠急性脊髓损伤（spinal cord injury，SCI）后细胞凋亡的作用和机制。

方法

采用雌性C 57 BL/6小鼠进行SCI造模，造模成功后使用随机法分为：脊髓损伤组（SCI组）、Electroacupuncture组（EA组）、Rosiglitazone组（R组），另设立假手术组（Sham组）。造模成功后对EA组小鼠取双侧“夹脊穴”和“足三里穴”进行电针，每日1次，连续治疗14 d；R组腹腔注射过氧化物酶体增殖物激活受体γ（peroxisome proliferator activated receptor γ，PPARγ）激动剂：Rosiglitazone（5 mg/kg），Sham及SCI组不予特殊干预。采用小鼠后肢运动功能评分系统（basso mouse scale，BMS）评分评价运动功能，HE染色法、免疫荧光法检测脊髓损伤后的病理改变，转录组测序（RNA sequencing，RNA-Seq）、定量蛋白质组学（tandem mass tag/isobaric tags for relative and absolute quantification，TMT/iTRAQ）技术检测电针作用的靶点及机制，Western blot法检测PPARγ、分化簇36（cluster of differentiation 36，CD36）、血红蛋白亚基α1（hemoglobin alpha，adult chain 1，Hba-a1）、血红蛋白β亚基（hemoglobin，beta adult t chain，Hbb-bt）、胱氨酸蛋白酶-3（Caspase-3，CASP3）蛋白表达水平。

结果

与SCI组相比，EA组和R组的后肢运动功能、组织结构和残存细胞数量均有改善。EA组和R组Caspase-3表达降低，PPARγ和CD36表达增加，EA组Hba-a1和Hbb-bt表达降低。此外，RNA-Seq、TMT/iTRAQ技术结果分析、韦恩分析及双组学联合分析确定了Hba-a1和Hbb-bt为电针作用的靶基因。KEGG通路富集分析表明电针被证明对PPAR信号通路有明显影响。

结论

电针可以通过调控PPARγ-CD36信号通路促进SCI后Hba-a1、Hbb-bt的清除，降低Caspase-3表达水平，减少细胞凋亡的发生，促进脊髓神经功能的恢复。

Abstract

Objective

To establish a mouse model of spinal cord injury （SCI），and to investigate the effect of electroacupuncture（EA） intervention on cell apoptosis after acute SCI and its mechanism.

Methods

Female C57BL/6 mice were used to establish a model of SCI，and after successful modeling，the mice were randomly divided into SCI group，EA group，and Rosiglitazone group（R group）；a sham-operation group（Sham group） was also established. After successful modeling，the mice in the EA group were given EA at bilateral Jiaji points and Zusanli once a day for 14 days，those in the R group were given intraperitoneal injection of the PPARγ agonist Rosiglitazone（5 mg/kg），and those in the Sham group and the SCI group were not given any specific treatment. BMS score was used to assess motor function；HE staining and immunofluorescence assay were used to observe pathological changes after SCI；RNA-Seq and TMT/iTRAQ techniques were used to identify the targets and mechanisms of EA；Western blot was used to measure the protein expression levels of PPARγ，CD36，Hba-a1，Hbb-bt，and caspase-3.

Results

Compared with the SCI group，the EA group and the R group had improvements in hindlimb motor function，tissue structure，and the number of surviving cells. The EA group and the R group had a significant reduction in the expression of caspase-3 and significant increases in the expression of PPARγ and CD36，and the EA group had significant reductions in the expression of Hba-a1 and Hbb-bt. In addition，RNA-Seq and TMT/iTRAQ techniques，significant analysis，Venn analysis，and dual-omics analysis identified Hba-a1 and Hbb-bt as the target genes of EA. The KEGG pathway enrichment analysis showed that EA had a significant effect on the PPAR signaling pathway.

Conclusion

By regulating the PPARγ-CD36 signaling pathway，EA can promote the clearance of Hba-a1 and Hbb-bt after SCI，reduce the expression level of caspase-3，alleviate cell apoptosis，and facilitate the recovery of spinal cord nerve function.

关键词

Keywords

references

GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators . Global，regional，and national burden of traumatic brain injury and spinal cord injury，1990-2016：a systematic analysis for the Global Burden of Disease Study 2016 [J ] . Lancet Neurol ， 2019 ， 18 （ 1 ）： 56 - 87 .

Ahuja CS ， Wilson JR ， Nori S ， et al . Traumatic spinal cord injury [J ] . Nat Rev Dis Primers ， 2017 ， 3 ： 17018 .

Sugeno A ， Piao WH ， Yamazaki M ， et al . Cortical transcriptome analysis after spinal cord injury reveals the regenerative mechanism of central nervous system in CRMP2 knock-in mice [J ] . Neural Regen Res ， 2021 ， 16 （ 7 ）： 1258 - 1265 .

Ding H ， Yu J ， Chang WJ ， et al . Searching for differentially expressed proteins in spinal cord injury based on the proteomics analysis [J ] . Life Sci ， 2020 ， 242 ： 117235 .

Morton AP ， Hadley JB ， Ghasabyan A ， et al . The α-globin chain of hemoglobin potentiates tissue plasminogen activator induced hyperfibrinolysis in vitro [J ] . J Trauma Acute Care Surg ， 2022 ， 92 （ 1 ）： 159 - 166 .

Sun Q ， Wu W ， Hu YC ， et al . Early releas e of high-mobility group box 1（HMGB1） from neurons in experimental subarachnoid hemorrhage in vivo and in vitro [J ] . J Neuroinflammation ， 2014 ， 11 ： 106 .

姚媛媛，张　鑫，赵丽明 , 等 . 高原相关高血压研究现状与展望 [J ] . 四川大学学报（医学版）， 2024 ， 55 （ 6 ）： 1454 - 1459 .

Yao YY ， Zhang X ， Zhao LL ， et al . Research Status and Prospects of Plateau-Related Hypertension [J ] . Journal of Sichuan University（Medical Edition）， 2024 ， 55 （ 6 ）： 1454 - 1459 .

Rainer TH ， Wong LKS ， Lam W ， et al . Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke [J ] . Clin Chem ， 2003 ， 49 （ 4 ）： 562 - 569 .

He YD ， Hua Y ， Keep RF ， et al . Hemoglobin expression in neurons and glia after intracerebral hemorrhage [J ] . Acta Neurochir Suppl ， 2011 ， 111 ： 133 - 137 .

Huang CC ， Chou CA ， Chen WY ， et al . Empagliflozin ameliorates free fatty acid induced-lipotoxicity in renal proximal tubular cells via the PPARγ/CD36 pathway in obese mice [J ] . Int J Mol Sci ， 2021 ， 22 （ 22 ）： 12408 .

Moore KJ ， Rosen ED ， Fitzgerald ML ， et al . The role of PPAR-gamma in macrophage differentiation and cholesterol uptake [J ] . Nat Med ， 2001 ， 7 （ 1 ）： 41 - 47 .

Shibuya-Fujiwara N ， Hirayama F ， Ogata Y ， et al . Phagocytosis in vitro of polyethylene glycol-modified liposome-encapsulated hemoglobin by human peripheral blood monocytes plus macrophages through scavenger receptors [J ] . Life Sci ， 2001 ， 70 （ 3 ）： 291 - 300 .

Shi ZJ ， Yuan SY ， Shi LL ， et al . Programmed cell death in spinal cord injury pathogenesis and therapy [J ] . Cell Prolif ， 2021 ， 54 （ 3 ）： e12992 .

Liu J ， Wu YC . Electro-acupuncture-modulated miR-214 prevents neuronal apoptosis by targeting Bax and inhibits sodium channel Nav1.3 expression in rats after spinal cord injury [J ] . Biomed Pharmacother ， 2017 ， 89 ： 1125 - 1135 .

Xin YY ， Wang JX ， Xu AJ . Electroacupuncture ameliorates neuroinflammation in animal models [J ] . Acupunct Med ， 2022 ， 40 （ 5 ）： 474 - 483 .

刘筱蔼，罗友根 . MiRNA调控脑缺血/再灌注诱导的自噬信号通路研究进展 [J ] . 中山大学学报（医学科学版）， 2024 ， 45 （ 1 ）： 21 - 27 .

Liu XA ， Luo YG . Research progress on MiRNA regulation of autophagy signaling pathway induced by cerebral ischemia/reperfusion [J ] . Journal of Sun Yat sen University（Medical Science Edition）， 2024 ， 45 （ 1 ）： 21 - 27 .

Conesa A ， Madrigal P ， Tarazona S ， et al . A survey of best practices for RNA-seq data analysis [J ] . Genome Biol ， 2016 ， 17 ： 13 .

Liu S ， Kang Y ， Zhang C ， et al . Isobaric tagging for relative and absolute protein quantification（iTRAQ）-based quantitative proteomics analysis of differentially expressed proteins 1 week after spinal cord injury in a rat model [J ] . Med Sci Monit ， 2020 ， 26 ： e924266 .

程　觅，张　雪，史阳琳，等 . 实验大鼠和小鼠穴位定位的研究概况 [J ] . 上海针灸杂志， 2021 ， 40 （ 5 ）： 640 - 646 .

Cheng M ， Zhang X ， Shi YL ， et al . A survey of acupoint location in experimental rats and mice [J ] . Shanghai J Acupunct Moxibustion ， 2021 ， 40 （ 5 ）： 640 - 646 .

Liu H ， Rose ME ， Culver S ， et al . Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats [J ] . Biochem Biophys Res Commun ， 2016 ， 472 （ 4 ）： 648 - 655 .

Li HP ， Zhang Q ， Yang XH ， et al . PPAR-γ agonist rosiglitazone reduces autophagy and promotes functional recovery in experimental traumaticspinal cord injury [J ] . Neurosci Lett ， 2017 ， 650 ： 89 - 96 .

Basso DM ， Fisher LC ， Anderson AJ ， et al . Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains [J ] . J Neurotrauma ， 2006 ， 23 （ 5 ）： 635 - 659 .

Rojas BE ， Hartman MD ， Figueroa CM ， et al . Proteolytic cleavage of Arabidopsis thaliana phosphoenolpyruvate carboxykinase-1 modifies its allosteric regulation [J ] . J Exp Bot ， 2021 ， 72 （ 7 ）： 2514 - 2524 .

Lisanti MP ， Scherer PE ， Vidugiriene J ， et al . Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source：implications for human disease [J ] . J Cell Biol ， 1994 ， 126 （ 1 ）： 111 - 126 .

Vasseur F ， Helbecque N ， Lobbens S ， et al . Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding（ ACDC ） gene promoter variants in morbid obesity：evidence for a role of ACDC in diabesity [J ] . Diabetologia ， 2005 ， 48 （ 5 ）： 892 - 899 .

Chmurzyńska A . The multigene family of fatty acid-binding proteins（FABPs）：function，structure and polymorphism [J ] . J Appl Genet ， 2006 ， 47 （ 1 ）： 39 - 48 .

Tran AP ， Warren PM ， Silver J . The biology of regeneration failure and success after spinal cord injury [J ] . Physiol Rev ， 2018 ， 98 （ 2 ）： 881 - 917 .

Turtle JD ， Henwood MK ， Strain MM ， et al . Engaging pain fibers after a spinal cord injury fosters hemorrhage and expands the area of secondary injury [J ] . Exp Neurol ， 2019 ， 311 ： 115 - 124 .

Jiang T ， Qin T ， Gao P ， et al . SIRT1 attenuates blood-spinal cord barrier disruption after spinal cord injury by deacetylating p66Shc [J ] . Redox Biol ， 2023 ， 60 ： 102615 .

de Campos Guerra JC ， Mourão MA ， França CN ， et al . Impact of coagulation in the development of thromboembolic events in patients with spinal cord injury [J ] . Spinal Cord ， 2014 ， 52 （ 4 ）： 327 - 332 .

Wang JL ， Luo X ， Liu L . Targeting CARD6 attenuates spinal cord injury（SCI） in mice through inhibiting apoptosis，inflammation and oxidative stress associated ROS production [J ] . Aging ， 2019 ， 11 （ 24 ）： 12213 - 12235 .

Fraussen J ， Beckers L ， van Laake-Geelen CCM ， et al . Altered circulating immune cell distribution in traumatic spinal cord injury patients in relation to clinical parameters [J ] . Front Immunol ， 2022 ， 13 ： 873315 .

Li C ， Wu ZR ， Zhou LQ ， et al . Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury [J ] . Sig Transduct Target Ther ， 2022 ， 7 ： 65 .

Viñals M ， Bermúdez I ， Llaverias G ， et al . Aspirin increases CD36，SR-BI，and ABCA1 expression in human THP-1 macrophages [J ] . Cardiovasc Res ， 2005 ， 66 （ 1 ）： 141 - 149 .

Shao GC ， Cao Y ， Chen ZL ， et al . How to use open-pFind in deep proteomics data analysis?—a protocol for rigorous identification and quantitation of peptides and proteins from mass spectrometry data [J ] . Biophys Rep ， 2021 ， 7 （ 3 ）： 207 - 226 .

Krishna S ， Cheng BK ， Sharma DR ， et al . PPAR-γ activation enhances myelination and neurological recovery in premature rabbits with intraventricular hemorrhage [J ] . Proc Natl Acad Sci U S A ， 2021 ， 118 （ 36 ）： e2103084118 .

Miao YM ， Zhang CL ， Yang L ， et al . The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα [J ] . Cell Commun Signal ， 2022 ， 20 （ 1 ）： 48 .

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