丙泊酚对TNF-α诱导的小胶质细胞HMGB1表达的调控作用

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摘要目的：研究丙泊酚对TNF-α诱导的小胶质BV-2细胞高迁移率族蛋白B1（HMGB1）表达的影响。方法：用不同浓度（5、10、20、50、100、150、200 μmol/L）的丙泊酚处理细胞后进行MTT实验检测细胞增殖；用不同浓度（5、10、20 ng/mL）的TNF-α处理细胞后进行RT-qPCR和Western blot检测HMGB1的表达；设立对照组、TNF-α（20 ng/mL）组、TNF-α（20 ng/mL）+丙泊酚（10、20、50 μmol/L）组，丙泊酚干预TNF-α处理的细胞进行RT-qPCR和Western blot检测HMGB1的表达和p38的酸化；利用siRNA沉默p38表达后再用丙泊酚处理，RT-qPCR和Western blot检测HMGB1的表达。结果：高浓度丙泊酚（150、200 μmol/L）抑制小胶质细胞增殖；与对照组比，经TNF-α刺激后小胶质细胞HMGB1表达增高；与TNF-α组比较，TNF-α+丙泊酚组HMGB1的表达明显降低，并呈剂量依赖性（P ＜0.05）；沉默p38表达可抑制TNF-α诱导小胶质细胞HMGB1的表达（P ＜0.05）；在沉默p38后再用丙泊酚处理，与单沉默p38比较，HMGB1的表达差异无统计学意义（P ＞0.05）。结论：丙泊酚可通过p38的激活调控TNF-α诱导小胶质细胞的HMGB1表达，从而影响脑损伤晚期炎症反应。

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关键词 ：丙泊酚, 小胶质BV-2细胞, TNF-&alpha, 高迁移率族蛋白B1

Abstract：Objective: To investigate the effect of propofol on the expression of HMGB1 of microglia BV-2 cells induced by TNF-α. Methods: MTT was used to detect cell proliferation of microglia treated by propofol in different concentrations (5, 10, 20, 50, 100, 150 and 200 μmol/L). Control group, TNF-α (20 ng/mL) group, and TNF-α (20 ng/mL) + propofol (10, 20 and 50 μmol/L) group were set up. The expression of HMGB1 and the phosphorylation of p38 in microglia were detected by RT-qPCR and Western blot after microglia was pretreated with propofol (10, 20 and 50 μmol/L) and then stimulated with TNF-α. Utilizing siRNA to silence p38 before it was treated with propofol and the expression of HMGB1 was examined by RT-qPCR and Western blot. Results:High concentration of propofol (150 and 200 μmol/L) inhibited the proliferation of microglial cells. Compared with the control group, the expression of HMGB1 was increased after TNF-α stimulation. The expression of
HMGB1 in TNF-α+propofol group was significantly reduced and presented dosage dependence compared with TNF-α group. Silencing p38 inhibited the TNF-α-induced expression of HMGB1 in microglia. There was no significant difference in HMGB1 expression between the group with silenced p38 alone and the propofol-treated group after silencing p38. Conclusion: Propofol can be used to regulate the expression of HMGB1 of microglial cells through activating p38 and thus affecting the advanced inflammatory response to brain injury.

Key words： propofol microglia BV-2 cells tumor necrosis factor alpha high mobility group protein B1

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https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I9/625

[1] 王曾庚, 杨春丽, 聂祥碧. 丙泊酚对急性肺损伤大鼠HMGB-1 表达的影响[J]. 南昌大学学报(医学版), 2014, 54(3): 10-12.
[2] LOTZE M T, TRACEY K J. High-mobility group box 1 protein(HMGB1): nuclear weapon in the immune arsenal[J].Nat Rev Immunol, 2005, 5(4): 331-342.
[3] 孙雪华, 曾邦雄. 丙泊酚的麻醉作用机制[J]. 临床麻醉学杂志, 2008, 24(4): 364-365.
[4] MERTENS M J, OLOFSEN E, ENGBERS F H, et al. Propofol reduces perioperative remifentanil requirements in a synergistic manner: response surface modeling of perioperative remifentanil-propofol interactions[J]. Anesthesiology,2003, 99(2): 347-359.
[5] 叶雪飞, 左春龙, 梅虹霞, 等. 丙泊酚对小胶质细胞炎症因子的影响及其机制研究[J]. 中国现代医学杂志, 2018, 28(2): 33-36.
[6] 王家强, 缪长虹, 陈家伟. 丙泊酚的脑保护作用及其机制研究进展[J]. 中国新药与临床杂志, 2016, 35(8): 538-541.
[7] JAWAN B, KAO Y H, GOTO S, et al. Propofol pretreatment attenuates LPS-induced granulocyte-macrophage colony-stimulating factor production in cultured hepatocytes by suppressing MAPK/ERK activity and NF-kappaB translocation[J]. Toxicol Appl Pharmacol, 2008, 229(3): 362-373.
[8] GUI B, SU M, CHEN J, et al. Neuroprotective effects of pretreatment with propofol in LPS-induced BV-2 microglia cells: role of TLR4 and GSK-3β[J]. Inflammation, 2012, 35(5): 1632-1640.
[9] ROUX P P, BLENIS J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions[J]. Microbiol Mol Biol Rev, 2004, 68(2): 320-344.
[10] SACCANI S, PANTANO S, NATOLI G. p38-dependent marking of inflammatory genes for increased NF-κB recruitment[J]. Nat Immunol, 2002, 3(1): 69-75.
[11] 王瑞珂, 张琴琴, 杨胜辉, 等. TNF-α通过p38 丝裂原活化蛋白激酶信号通路对小胶质细胞HMGB I表达的调控作用[J]. 中南大学学报(医学版), 2015, 40(9): 967-972.
[12] RICE R A, PHAM J, LEE R J, et al. Microglial repopulation resolves inflammation and promotes brain recovery after injury[J]. Glia, 2017, 65(6): 931-944.
[13] 王新, 李明军, 张坤, 等. 脑出血与小胶质细胞介导的炎症相关性[J]. 中国老年学杂志, 2013, 33(13): 3268-3270.
[14] 蒋奕红, 谢景远, 熊威威, 等. 血清S100β蛋白水平与丙泊酚及依托咪酯麻醉后幼儿早期认知功能障碍的相关性研究[J]. 医学研究生学报, 2015(8): 824-828.
[15] KIRKPATRICK T, COCKSHOTT I D, DOUGLAS E J, et al. Pharmacokinetics of propofol (diprivan) in elderly patients[J]. Br J Anaesth, 1988, 60(2): 146-150.
[16] 孙雪华, 曾邦雄. 丙泊酚的麻醉作用机制[J]. 临床麻醉学杂志, 2008, 24(4): 364-365.
[17] FRANK M G, WEBER M D, FONKEN L K, et al. The redox state of the alarmin HMGB1 is a pivotal factor in neuroinflammatory and microglial priming: A role for the NLRP3 inflammasome[J]. Brain Behav Immun, 2016, 55: 215-224.
[18] ANDERSSON U, TRACEY K J. HMGB1 is a therapeutic target for sterile inflammation and infection[J]. Annu Rev Immunol, 2011, 29: 139-162.
[19] 李世朋, 何金丹, 于瑶, 等. 缺血再灌注诱导小鼠肝细胞释放高迁移率族蛋白B1对P38MAPK信号通路的影响[J]. 中华肝胆外科杂志, 2016, 22(4): 273-276.
[20] KIM H S, PARK E J, PARK S W, et al. A tetrahydroisoquinoline alkaloid THI-28 reduces LPS-induced HMGB1 and diminishes organ injury in septic mice through p38 and PI3K/ Nrf2/HO-1 signals[J]. Int Immunopharmacol, 2013, 17(3):684-692.