人参皂苷Rg1通过抑制NLRP3炎症小体途径减轻氧糖剥夺/复供后小胶质细胞炎症反应

doi:10.13418/j.issn.1001-165x.2024.1.07

Abstract

Abstract: Objective To investigate the effect of ginsenoside Rg1 on the inflammatory response of microglia cells after oxygen-glucose deprivation/resupply injury through NLRP3 inflammasome pathway, and to further investigate its anti-inflammatory mechanism. Methods BV-2 microglia were randomly divided into six groups: No treatment group (Con), oxygen glucose deprivation/resupply group (OGD/R), ginsenoside Rg1 low, medium and high dose groups (0.1, 0.2, 0.4 mmol/L, Rg1L, Rg1M, Rg1H), MCC950 control group (0.05 mmol/L, MCC950). The cell proliferation was detected by CCK8. Immunofluorescence and western blotting were used to detect the expression of NLRP3 inflammasome-related protein in BV-2 microglia after treatment with different concentrations of ginsenoside Rg1 and MCC950 for 48 h. The expression levels of IL-1β and IL-18 in BV-2 microglia were detected by ELISA. Results Compared with Con group, Iba-1 green fluorescence was observed in the cytoplasm of BV-2 microglia cells treated with hypoxia and glucose deficiency/resupply. After OGD/R treatment of BV-2 microglia for 2h, the proliferation rate of BV-2 microglia cells showed an obvious downward trend after 48 h culture with different concentrations of ginsenoside Rg1 and MCC950. There were significant positive expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the OGD/R group. The NLRP3 protein expression in Rg1L, Rg1M and Rg1H groups was significantly decreased, and the expression decreased with the increasing of drug concentration. The results showed that compared with OGD/R group, ginsenoside Rg1 and MCC950 inhibited the expression of NLRP3 in activated BV-2 microglia cells (P<0.01). Conclusions Ginsenoside Rg1 may inhibit the expression levels of IL-1β and IL-18, thus inhibiting the inflammatory response by inhibiting the expressions of NLRP3, ASC, Caspase-1 and interfering with NLRP3 inflammasome synthesis.

Key words: Ginsenoside Rg1; , , Oxygen and glucose deprivation/resupply; , , Microglia; , , Inflammation; , , NLRP3

CLC Number:

R285.5

Wang Xinghang, Ding Jiayuan, Li Fang, Bao Cuifen, Yan Lijing. Ginsenoside Rg1 reduces the inflammatory response of microglia after oxygen glucose deprivation/resupply by inhibiting the NLRP3 inflammasome pathway[J]. Chinese Journal of Clinical Anatomy, 2024, 42(1): 33-41.

References 28

[1]	Cao Y, Gao W, Tang H, et al. Long non-coding RNA TALNEC2 aggravates cerebral ischemia/ reperfusion injury via acting as a competing endogenous RNAs for miR-650 to target apoptotic peptidase activating factor 1[J].Neuroscience, 2021, 458:64-76. DOI:10.1016/j.neuroscience.2020.10.010.
[2]	Nazarinia D, Sharifi M, Dolatshahi M, et al. FoxO1 and Wnt/β-catenin signaling pathway: Molecular targets of human amniotic mesenchymal stem cells-derived conditioned medium (hAMSC-CM) in protection against cerebral ischemia/reperfusion injury[J]. J Chem Neuroanat, 2021, 112:101918. DOI:10.1016/j.jchemneu.2021.101918.
[3]	Jurcau A, Simion A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion injuries: from pathophysiology to therapeutic strategies[J]. Int J Mol Sci, 2021, 23(1):14.DOI:10.3390/ijms 2301001 4.
[4]	Chen C, Chen W, Nong Z, et al. Hyperbaric oxygen alleviated cognitive impairments in mice induced by repeated cerebral ischemia-reperfusion injury via inhibition of autophagy[J]. Life Sci, 2020, 241:117170. DOI:10.1016/j.lfs. 2019.117170.
[5]	录亚鹏, 谢建琴. NLRP3炎性小体在缺血再灌注损伤治疗中作用的研究进展[J]. 基础医学与临床, 2023, 43(4):706-710. DOI:10.16352/j.issn. 1001-6325.2023.04.0706.
[6]	武文文, 吴诗卉, 刘春红, 等. 人参皂苷Rg_1对局灶性脑缺血再灌注损伤模型大鼠的预防作用及机制研究[J].中国药房, 2020, 31(11):1287-1293. DOI: 10.6039/j.issn. 1001-0408.2020.11.02.
[7]	Cao X , Wang Y , Gao L .CHRFAM7A overexpression attenuates cerebral ischemia-reperfusion injury via inhibiting microglia pyroptosis mediated by the NLRP3/Caspase-1 pathway[J]. Inflammation, 2021, 44(3): 1023-1034. DOI: 10.1007/s10753-020 -01398-4.
[8]	Pei H, Du R, He Z, et al. Protection of a novel velvet antler polypeptide PNP1 against cerebral ischemia-reperfusion injury [J]. Int J Biol Macromol, 2023, 247:125815.DOI：10.1016/J.IJBIOMAC. 2023. 125815.
[9]	Li J , Xu P , Hong Y ,et al.Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury[J]. J Neuroin flammation, 2023, 20(1):148. DOI:10.1186/s 12974-023-02819-5.
[10]	Paolicelli RC, Sierra A, Stevens B, et al. Microglia states and nomenclature: A field at its crossroads [J].Neuron, 2022,110(21):3458-3483. DOI: 10.1016/j.neuron.2022.10.020.
[11]	Xiao L , Wei F , Zhou Y , et al. Dihydrolipoic acid-gold nanoclusters regulate microglial polarization and have the potential to alter neurogenesis[J]. Nano Lett, 2020, 20(1): 478-495. DOI:10.1021/acs.nanolett.9b04216.
[12]	Qiu Z, Lu P, Wang K, et al. Dexmedetomidine inhibits neuroinflammation by altering microglial M1/M2 polarization through MAPK/ERK pathway[J]. Neurochem Res, 2020, 45(2):345-353. DOI:10.1007/s11064-019-02922-1.
[13]	玉苏甫·马合木提,阿布都热合曼·阿卜拉,苏日青,等. 抑制转位蛋白在氧糖剥夺/复糖复氧模型中对BV-2细胞损伤和自噬的影响[J].中国药理学通报, 2022, 38(5):761-766. DOI:10.12360/CPB202108096.
[14]	Shen HP, Pei HY, Zhai LP, et al. Salvianolic acid C improves cerebral ischemia reperfusion injury through suppressing microglial cell M1 polarization and promoting cerebral angiogenesis [J]. Int Immunopharmacol, 2022, 110:109021. DOI：10.1016/J.INTIMP. 2022. 109021.
[15]	Yuyou H, Shengpan C, Yumin L, et al. Crosstalk between inflammation and the BBB in stroke[J]. Curr Neuropharmacol, 2020,18(12):1227-1236 . DOI：10.2174/1570159X18666200620230321.
[16]	刘春红, 吴诗卉, 武文文, 等. 人参皂苷Rg1抑制脑缺血再灌注细胞坏死的实验研究[J]. 重庆医学, 2020, 49(21):3515-3519. DOI:10.3969/j.issn.1671-8348.2020.21.003.
[17]	Zhang W , Song J , Li W ,et al. Salvianolic acid D alleviates cerebral ischemia-reperfusion injury by suppressing the cytoplasmic translocation and release of HMGB1-triggered NF-κB activation to inhibit inflammatory response[J]. Mediators Inflamm, 2020, 2020:9049614. DOI:10.1155/2020/9049614.
[18]	He S, Liu R, Li B, et al. Propagermanium, a CCR2 inhibitor, attenuates cerebral ischemia/reperfusion injury through inhibiting inflammatory response induced by microglia[J]. Neurochem Int, 2019: 125: 99-110. DOI:10.1016/j.neuint. 2019.02.010.
[19]	Ye Y , Jin T , Zhang X , et al. Meisoindigo Protects Against Focal Cerebral Ischemia-Reperfusion Injury by Inhibiting NLRP3 Inflammasome Activation and Regulating Microglia/ Macrophage Polarization via TLR4/NF-κB Signaling Pathway[J].Front CellNeurosci, 2019,13:553. DOI: 10.3389/ fncel.2019.00553.
[20]	Gaire BP , Song MR , Choi JW .Sphingosine 1-phosphate receptor subtype 3 (S1P3) contributes to brain injury after transient focal cerebral ischemia via modulating microglial activation and their M1 polarization[J]. J Neuroinflammation, 2018, 15(1): 284. DOI:10.1186/s12974-018-1323-1.
[21]	Zheng Y, He R, Wang P, et al. Exosomes from LPS-stimulated macrophages induce neuroprotection and functional improve -ment after ischemic stroke by modulating microglial polarization[J]. Biomater Sci, 2019,7(5): 2037-2049. DOI:10.1039/ c8bm01449c.
[22]	Zhao Y , Gan Y , Xu G , et al. MSCs-derived exosomes attenuate acute brain injury and inhibit microglial inflammation by reversing CysLT2R- ERK1/2 mediated microglia M1 polarization[J]. Neurochem Res, 2020, 45(5):1180-1190. DOI:10.1007/s11064-020-02998-0.
[23]	Li QQ , Ding DH , Wang XY ,et al. Lipoxin A4 regulates microglial M1/M2 polarization after cerebral ischemia- reperfusion injury via the Notch signaling pathway[J]. Exp Neurol, 2021, 339:113645. DOI:10.1016/j.expneurol. 2021.113645.
[24]	Wang T, Zhao N , Peng L , et al. DJ-1 regulates microglial polarization through P62-mediated TRAF6/IRF5 signaling in cerebral ischemia- reperfusion[J]. Front Cell Dev Biol, 2020, 8:593890. DOI:10.3389/fcell.2020. 593890.
[25]	Yang CJ, Li X, Feng XQ, et al. Activation of LRP1 ameliorates cerebral ischemia/ reperfusion injury and cognitive decline by suppressing neuroinflammation and oxidative stress through TXNIP/NLRP3 signaling pathway in mice [J].Oxid Med Cell Longev, 2022, 2022:8729398. DOI: 10.1155/2022/8729398.
[26]	Wang L, Ren W, Wu Q, et al. NLRP3 inflammasome activation: A therapeutic target for cerebral ischemia- reperfusion injury [J]. Front Mol Neurosci, 2022, 15:847440. DOI: 10.3389/fnmol.2022.847440.
[27]	Prakash R, Vyawahare A, Sakla R, et al. NLRP3 inflammasome-targeting nanomicelles for preventing ischemia-reperfusion-induced inflammatory injury. [J]. ACS Nano, 2023, 17(9): 8680-8693. DOI: 10.1021/acsnano.3c01760.
[28]	Franke M, Bieber M, Kraft P, et al. The NLRP3 inflammasome drives inflammation in ischemia/reperfusion injury after transient middle cerebral artery occlusion in mice[J].Brain Behav Immun, 2021, 92:223-233. DOI: 10.1016/j.bbi. 2020.12.009.

Ginsenoside Rg1 reduces the inflammatory response of microglia after oxygen glucose deprivation/resupply by inhibiting the NLRP3 inflammasome pathway

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