短链脂肪酸对大鼠脊髓缺血再灌注损伤时小胶质细胞M1/M2型极化的影响

doi:10.20047/j.issn1673-7210.2023.23.04

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Abstract Objective To investigate the effect of short-chain fatty acids (SCFA) on M1/M2 polarization of microglia during spinal cord ischemia reperfusion injury (IRI) in rats. Methods A total of 72 healthy male SD rats with SPF grade, aged 6 to 8 weeks and weight 200 to 250 g, were divided into sham operation group (group S), IRI group, SCFA group and SCFA+ free fatty acid receptor type 2 (FFAR2) blocker GLPG0974 group (GLPG group) by random number table method, with 18 rats in each group. The drinking water of SCFA group and GLPG group contained 25.9 mmol/L sodium acetate, 40.0 mmol/L sodium propionate and 67.5 mmol/L sodium butyrate, and the drinking water of S group and IRI group contained 133.4 mmol/L sodium chloride. After four weeks, IRI model was established in IRI group, SCFA group, and GLPG group, sham operation was performed in S group. In the GLPG group, 2 mg/kg GLPG0974 was intraperitoneally injected immediately after reperfusion and at the 1st to 6th day of reperfusion, and corresponding water was continuously supplied during the reperfusion period. Hind limb behavioral scores were performed at 1, 3, 5, and 7 days after reperfusion. Blood-spinal cord barrier (BSCB) permeability, spinal neuron survival rate, acetic acid, propionic acid, and butyric acid concentrations in stool and cerebrospinal fluid were measured at 7 d after reperfusion. The levels of spinal cord microglia differentiation cluster (CD) 86, CD206, and spinal tumor necrosis factor-α (TNF-α), interleukin(IL)-1β, IL-4, phosphorylated nuclear factor κB p65 (p-NF-κB p65), and phosphorylated signal transduction and transcriptional activator 3 (p-STAT3) were detected. Results Compared with S group, the behavioral score of the posterior limb, neuronal survival rate, acetic acid, propionic acid, and butyric acid concentrations in stool and cerebrospinal fluid were decreased in IRI group, while BSCB permeability, CD86, TNF-α, IL-1β, and P-NF-κB p65 were increased (P＜0.01). Compared with IRI group, the behavioral score, neuronal survival rate, acetic acid, propionic acid, and butyric acid concentrations in stool and cerebrospinal fluid in SCFA group were increased, BSCB permeability, CD86, TNF-α, IL-1β, and P-NF-κB p65 were decreased, while CD206, IL-4, and P-Stat3 were increased (P＜0.01). Compared with SCFA group, there was no significant difference in the concentrations of acetic acid, propionic acid, and butyric acid in stool and cerebrospinal fluid of GLPG group (P＞0.05). Conclusion SCFA can promote M1-type to M2-type polarization of microglia in rat spinal cord during IRI and reduce inflammation.

Key words： Short chain fatty acids Spinal cord Reperfusion injury Microglia M1/M2 polarization

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	WANG Liping LI Fan ZHOU Kunming LIN Simeng

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WANG Liping LI Fan ZHOU Kunming LIN Simeng. Effect of short-chain fatty acids on M1/M2 polarization of microglia during spinal cord ischemia-reperfusion injury in rats[J]. 中国医药导报, 2023, 20(23): 23-27.

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https://www.yiyaodaobao.com.cn/EN/10.20047/j.issn1673-7210.2023.23.04 OR https://www.yiyaodaobao.com.cn/EN/Y2023/V20/I23/23

[1] Wang L，Yao Y，He R，et al. Methane ameliorates spinal cord ischemia-reperfusion injury in rats：Antioxidant，anti-inflammatory and anti-apoptotic activity mediated by Nrf2 activation [J]. Free Radic Biol Med，2017，103：69-86.
[2] 王丽萍，郭晓明，高贤伟，等.低氧预处理对大鼠骨髓间充质干细胞抗炎效应的影响：离体和在体实验[J].中华麻醉学杂志，2013，33（11）：1300-1305.
[3] 曾昭恺，薛海燕，王丽萍.甲烷对脊髓缺血再灌注大鼠炎症反应时P2X7R/NLRP3信号通路的影响[J].中华麻醉学杂志，2020，40（2）：225-228.
[4] Liu W，Rong Y，Wang J，et al. Exosome-shuttled miR-216a- 5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization [J]. J Neuroinflammation，2020，17（1）：47.
[5] Orihuela R，McPherson CA，Harry GJ. Microglial M1/M2 polarization and metabolic states [J]. Br J Pharmacol，2016，173（4）：649-665.
[6] Lee J，d’Aigle J，Atadja L，et al. Gut microbiota-derived short-chain fatty acids promote post-stroke recovery in aged mice [J]. Circ Res，2020，127（4）：453-465.
[7] Jing Y，Yu Y，Bai F，et al. Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model：involvement of brain-gut axis [J]. Microbiome，2021，9（1）：59.
[8] Yang LL，Millischer V，Rodin S，et al. Enteric short-chain fatty acids promote proliferation of human neural progenitor cells [J]. J Neurochem，2020，154（6）：635-646.
[9] Sadler R，Cramer JV，Heindl S，et al. Short-chain fatty acids improve poststroke recovery via immunological mechanisms [J]. J Neurosci，2020，40（5）：1162-1173.
[10] Zhou F，Wang X，Han B，et al. Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization [J]. Mol Pain，2021，17：17448069219 96520.
[11] Wenzel TJ，Gates EJ，Ranger AL，et al. Short-chain fatty acids （SCFAs） alone or in combination regulate select immune functions of microglia-like cells [J]. Mol Cell Neurosci，2020， 105：103493.
[12] 江振作，刘晓雷，王跃飞，等.Beagle犬脑脊液-血浆-粪便中短链脂肪酸分析[J].药物分析杂志，2015，35（4）：600-604.
[13] Kigerl KA，Hall JC，Wang L，et al. Gut dysbiosis impairs recovery after spinal cord injury [J]. J Exp Med，2016，213（12）：2603-2620.
[14] Kigerl KA，Mostacada K，Popovich PG. Gut microbiota are disease-modifying factors after traumatic spinal cord injury [J]. Neurotherapeutics，2018，15（1）：60-67.
[15] Pierre K，Pellerin L. Monocarboxylate transporters in the central nervous system：distribution，regulation and function [J]. J Neurochem，2005，94（1）：1-14.
[16] Li M，van Esch BCAM，Wagenaar GTM，et al. Pro- and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells [J]. Eur J Pharmacol，2018，832：52-59.
[17] Kim S，Kim JH，Park BO，et al. Perspectives on the therapeutic potential of short-chain fatty acid receptors [J]. BMB Rep，2014，47（3）：173-178.
[18] Ulven T. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets [J]. Front Endocrinol （Lausanne），2012，3：111.
[19] Ying XD，Wei G，An H. Sodium butyrate relieves lung ischemia-reperfusion injury by inhibiting NF-κB and JAK2/ STAT3 signaling pathways [J]. Eur Rev Med Pharmacol Sci，2021，25（1）：413-422.
[20] Wang RX，Li S，Sui X. Sodium butyrate relieves cerebral ischemia-reperfusion injury in mice by inhibiting JNK/ STAT pathway [J]. Eur Rev Med Pharmacol Sci，2019，23（4）： 1762-1769.
[21] Qiao Y，Qian J，Wang F，et al. Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear factor kappa B activation in Kupffer cells [J]. J Surg Res，2014，187（2）：653-659.
[22] Luo QJ，Sun MX，Guo YW，et al. Sodium butyrate protects against lipopolysaccharide-induced liver injury partially via the GPR43/β-arrestin-2/NF-κB network [J]. Gastroenterol Rep （Oxf），2020，9（2）：154-165.
[23] Lee SU，In HJ，Kwon MS，et al. β-Arrestin 2 mediates G protein-coupled receptor 43 signals to nuclear factor-κB [J]. Biol Pharm Bull，2013，36（11）：1754-1759.
[24] Kobashi S，Terashima T，Katagi M，et al. Transplantation of M2-deviated microglia promotes recovery of motor function after spinal cord injury in mice [J]. Mol Ther，2020，28（1）：254-265.
[25] Chen S，Ye J，Chen X，et al. Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3 [J]. J Neuroinflammation，2018，15（1）：150.