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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摘要目的探讨短链脂肪酸（SCFA）对大鼠脊髓缺血再灌注损伤（IRI）时小胶质细胞M1/M2型极化的影响。方法 SPF级健康雄性SD大鼠72只，6～8周龄，体重200～250 g，采用随机数字表法分为假手术组（S组）、IRI组、SCFA组和SCFA+游离脂肪酸受体2型（FFAR2）阻滞剂GLPG0974组（GLPG组），每组18只。SCFA组和GLPG组饮水中含有25.9 mmol/L乙酸钠、40.0 mmol/L丙酸钠和67.5 mmol/L丁酸钠，S组和IRI组饮水中含有133.4 mmol/L氯化钠；4周后IRI组、SCFA组和GLPG组建立脊髓IRI模型，S组实施假手术；GLPG组于再灌注即刻和再灌注第1～6天时腹腔注射2 mg/kg GLPG0974，再灌注期持续供应相应饮水。再灌注1、3、5、7 d时行后肢行为学评分，再灌注7 d时检测血-脊髓屏障（BSCB）通透性、脊髓神经元存活率，粪便和脑脊液乙酸、丙酸、丁酸浓度，脊髓小胶质细胞分化簇（CD）86、CD206及脊髓肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-4、磷酸化核因子κB p65（p-NF-κB p65）和磷酸化信号转导与转录激活因子3（p-STAT3）表达水平。结果与S组比较，IRI组后肢行为学评分，神经元存活率，粪便和脑脊液乙酸、丙酸、丁酸浓度降低，BSCB通透性、CD86、TNF-α、IL-1β、p-NF-κB p65升高（P＜0.01）；与IRI组比较，SCFA组后肢行为学评分，神经元存活率，粪便和脑脊液乙酸、丙酸、丁酸浓度升高，BSCB通透性、CD86、TNF-α、IL-1β、p-NF-κB p65降低，CD206、IL-4、p-STAT3升高（P＜0.01）；与SCFA组比较，GLPG组粪便和脑脊液乙酸、丙酸、丁酸浓度差异无统计学意义（P＞0.05）。结论 SCFA可促进大鼠脊髓IRI时小胶质细胞M1型向M2型极化，减轻炎症反应。

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	王丽萍　　李帆　　周坤明　　林斯梦

关键词 ：短链脂肪酸, 脊髓, 再灌注损伤, 小胶质细胞, M1/M2型极化

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

基金资助:福建省科技对外合作项目（2020I0035）；
联勤保障部队第九〇〇医院战创伤救治专项（2022ZL04）；
福建医科大学教育教学研究项目（J22065）。

作者简介: 王丽萍（1979.7-），女，医学博士，博士后，副主任医师，副教授，硕士生导师，主要从事围手术期神经系统保护与镇痛研究。

引用本文:

王丽萍　　李帆　　周坤明　　林斯梦. 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[J]. 中国医药导报, 2023, 20(23): 23-27.
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. 中国医药导报, 2023, 20(23): 23-27.

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