丙泊酚对缺血性脑损伤脑保护作用机制的研究进展
黄蕊 刘志刚▲
武汉大学人民医院麻醉科,湖北武汉 430060
Research progress on the protective mechanism of Propofol on ischemic brain injury
HUANG Rui LIU Zhigang▲
Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China
摘要 缺血性脑损伤(IBI)是成人致残的主要原因之一,IBI引起神经炎症反应、氧化应激反应及细胞凋亡等使神经元受损,且IBI目前治疗手段有限。作为临床常用静脉麻醉药,丙泊酚除具有镇静催眠作用外,还具有减少脑血流、降低大脑新陈代谢的作用,其可通过磷酸肌醇3激酶(PI3K)/丝氨酸-苏氨酸蛋白激酶(Akt)通路及Toll样受体4(TLR4)/核因子(NF)-κB通路发挥抗炎作用,减少氧自由基产生以及对抗细胞凋亡等作用在缺血脑组织及神经元中发挥保护作用。丙泊酚的脑保护作用可能成为临床上治疗IBI的新靶点。
关键词 :
丙泊酚 ,
缺血性脑损伤 ,
炎症反应 ,
氧化应激
Abstract :Ischemic brain injury (IBI) is one of the main causes of adult disability. IBI causes neuro-inflammation, oxidative stress and cell apoptosis to damage neurons, and current treatments for IBI are limited. As a commonly used intravenous anesthetic in clinical practice, in addition to its sedative and hypnotic effects, Propofol also has the effects of reducing cerebral blood flow and lowering brain metabolism. It can be passed through phosphoinositide 3-kinase (PI3K)/serine-threonine protein kinase (Akt) pathway and Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway play an anti-inflammatory effect, reduce the production of oxygen free radicals and resist cell apoptosis, and play a protective role in ischemic brain tissue and neurons. The protective effect of Propofol may become a new target for clinical treatment of IBI.
Key words :
Propofol
Ischemic brain injury
Inflammatory response
Oxidative stress
基金资助: 湖北省自然科学基金资助项目(2015CKB761)。
通讯作者:
▲通讯作者
[1] Li X,Yao L,Liang Q,et al. Propofol Protects Hippocampal Neurons from Hypoxia-Reoxygenation Injury by Decreasing Calcineurin-Induced Calcium Overload and Activating YAP Signaling [J]. Oxid Med Cell Longev,2018, 2018:1725191.
[2] Zheng Y,Bu J,Yu L,et al. Nobiletin improves propofol-induced neuroprotection via regulating Akt/mTOR and TLR 4/NF-kappa B signaling in ischemic brain injury in rats [J]. Biomed Pharmacother,2017,91:494-503.
[3] Hausburg MA,Banton KL,Roman PE,et al. Effects of propofol on ischemia-reperfusion and traumatic brain injury [J]. J Crit Care,2020,56:281-287.
[4] Chen CY,Tsai YF,Huang WJ,et al. Propofol inhibits endogenous formyl peptide-induced neutrophil activation and alleviates lung injury [J]. Free Radic Biol Med,2018, 129:372-382.
[5] 谢桂玲,李浩波,夏正远,等.异丙酚后处理对糖尿病性心肌细胞缺氧复氧损伤时坏死性凋亡的影响[J].中华麻醉学杂志,2018,38(3):296-299.
[6] Zheng G,Qu H,Li F,et al. Propofol attenuates sepsis-induced acute kidney injury by regulating miR-290-5p/CCL-2 signaling pathway[J]. Braz J Med Biol Res,2018, 51(11):e7655.
[7] Jayaraj RL,Azimullah S,Beiram R,et al. Neuroinflammation:friend and foe for ischemic stroke [J]. J Neuroinflammation,2019,16(1):142.
[8] Rocha-Ferreira E,Sisa C,Bright S,et al. Curcumin:Novel Treatment in Neonatal Hypoxic-Ischemic Brain Injury [J]. Front Physiol,2019,10:1351.
[9] Le K,Daliv EC,Wu S,et al. SIRT1-regulated HMGB1 release is partially involved in TLR4 signal transduction:A possible anti-neuroinflammatory mechanism of resveratrol in neonatal hypoxic-ischemic brain injury [J]. Int Immunopharmacol,2019,75:105779.
[10] 朱丹,汪立刚,徐蕾.紫草素对缺血性脑损伤大鼠脑组织保护作用的研究[J].解放军医药杂志,2019,31(7):1-4.
[11] Jiang X,Andjelkovic AV,Zhu L,et al. Blood-brain barrier dysfunction and recovery after ischemic stroke [J]. Prog Neurobiol,2018:144-171.
[12] Zhao Y,Yan F,Yin J,et al. Synergistic Interaction Between Zinc and Reactive Oxygen Species Amplifies Ischemic Brain Injury in Rats [J]. Stroke,2018,49(9):2200-2210.
[13] Rehni AK,Shukla V,Perez-Pinzon MA,et al. Acidosis mediates recurrent hypoglycemia-induced increase in ischemic brain injury in treated diabetic rats [J]. Neuropharmacology,2018,135:192-201.
[14] Zhang T,Wu C,Yang X,et al. Pseudoginsenoside-F11 Protects against Transient Cerebral Ischemia Injury in Rats Involving Repressing Calcium Overload [J]. Neuroscience,2019,411:86-104.
[15] Fels JA,Manfredi G. Sex Differences in Ischemia/Reperfusion Injury:The Role of Mitochondrial Permeability Transition [J]. Neurochem Res,2019,44(10):2336-2345.
[16] Radak D,Katsiki N,Resanovic I,et al. Apoptosis and Acute Brain Ischemia in Ischemic Stroke [J]. Curr Vasc Pharmacol,2017,15(2):115-122.
[17] 闫凤,孙鹏,赵会寿,等.支链氨基酸对大鼠局灶性缺血后神经元凋亡的影响[J].中华临床营养杂志,2019,27(2):118-122.
[18] Uzdensky AB. Apoptosis regulation in the penumbra after ischemic stroke:expression of pro- and antiapoptotic proteins [J]. Apoptosis,2019,24(9/10):687-702.
[19] Yang Q,Jiang W,Hou P. Emerging role of PI3K/AKT in tumor-related epigenetic regulation [J]. Semin Cancer Biol,2019,59:112-124.
[20] Zhang HB,Tu XK,Chen Q,et al. Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage:Involvement of PI3K/Akt Pathway [J]. J Stroke Cerebrovasc Dis,2019:104375.
[21] 涂献坤,杨滨,涂德文,等.PI3K/Akt通路在丙泊酚减轻大鼠脑缺血性损伤中的作用[J].中国药理学通报,2019,35(5):630-633.
[22] Qin X,Sun ZQ,Zhang XW,et al. TLR4 signaling is involved in the protective effect of propofol in BV2 microglia against OGD/reoxygenation [J]. J Physiol Biochem,2013,69(4):707-718.
[23] Zheng X,Huang H,Liu J,et al. Propofol Attenuates Inflammatory Response in LPS-Activated Microglia by Regulating the miR-155/SOCS1 Pathway [J]. Inflammation,2018,41(1):11-19.
[24] Ma J,Xiao W,Wang J,et al. Propofol Inhibits NLRP3 Inflammasome and Attenuates Blast-Induced Traumatic Brain Injury in Rats [J]. Inflammation,2016,39(6):2094-2103.
[25] Irwin MG,Chung CKE,Ip KY,et al. Influence of propofol-based total intravenous anaesthesia on peri-operative outcome measures:a narrative review [J]. Anaesthesia,2020,75(Suppl 1):e90-e100.
[26] Yu QJ,Yang Y. Function of SOD1,SOD2,and PI3K/AKT signaling pathways in the protection of propofol on spinal cord ischemic reperfusion injury in a rabbit model [J]. Life Sci,2016,148:86-92.
[27] Liu XR,Cao L,Li T,et al. Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes [J]. Apoptosis,2017,22(5):639-646.
[28] Wang Y,Tian D,Wei C,et al. Propofol Attenuates alpha-Synuclein Aggregation and Neuronal Damage in a Mouse Model of Ischemic Stroke [J]. Neurosci Bull,2020,36(3):289-298.
[29] Yao W,Han X,Zhang Y,et al. Intravenous Anesthetic Protects Hepatocyte from Reactive Oxygen Species-Induced Cellular Apoptosis during Liver Transplantation In Vivo [J]. Oxid Med Cell Longev,2018,2018:4780615.
[30] Wang H,Zheng S,Liu M,et al. The Effect of Propofol on Mitochondrial Fission during Oxygen-Glucose Deprivation and Reperfusion Injury in Rat Hippocampal Neurons [J]. PLoS One,2016,11(10):e0165052.
[1]
韩广弢 李皓桓 蔡伟松 张宇标. 骨关节炎中的氧化应激信号通路研究进展 [J]. 中国医药导报, 2020, 17(9): 29-32.
[2]
韦婷艳1,2 杨杰3 曾宇婷4 黄绮亭4 刘钰君4. NLRP3炎症小体和氧化应激在新生儿缺氧缺血性脑病患者胎盘组织中的表达及其临床意义 [J]. 中国医药导报, 2020, 17(8): 17-20.
[3]
李芳芳 张琪. 川芎嗪对血管内皮损伤的保护作用机制研究进展 [J]. 中国医药导报, 2020, 17(8): 25-28.
[4]
张坤1 柯山2. 七氟醚复合丙泊酚对肝硬化患者术后免疫功能、肝肾功能的影响 [J]. 中国医药导报, 2020, 17(7): 111-115,119.
[5]
程阳阳 孔维佳. 天麻素防治缺血性脑损伤的机制研究进展 [J]. 中国医药导报, 2020, 17(6): 48-52.
[6]
张晗 吴林玲 闫颖. 多囊卵巢综合征氧化应激及标志物的研究进展 [J]. 中国医药导报, 2020, 17(5): 31-34.
[7]
周玮1,2 姜淑娟3. 大气细颗粒物污染与慢性阻塞性肺疾病气道炎症和氧化应激关系研究 [J]. 中国医药导报, 2020, 17(5): 125-128.
[8]
刘海涛 葛伟. 乙醛脱氢酶2在阿尔茨海默病中的研究进展 [J]. 中国医药导报, 2020, 17(4): 36-39.
[9]
赵艳红 李红梅 孙阳. 高通量血液透析联合海昆肾喜对糖尿病肾病患者氧化应激及微炎症状态的影响 [J]. 中国医药导报, 2020, 17(4): 98-101,109.
[10]
王怡茹 张一凡 刘萍. 免疫细胞参与动脉粥样硬化炎症反应的研究进展 [J]. 中国医药导报, 2020, 17(35): 46-48,52.
[11]
李燕梅1 郝金平1 赵宇宏2. 克洛己新干混悬剂治疗小儿慢性咳嗽的效果 [J]. 中国医药导报, 2020, 17(35): 92-95.
[12]
史媛 董贝贝 于泳浩▲. 胃肠内镜检查中镇静镇痛药物应用的研究进展 [J]. 中国医药导报, 2020, 17(34): 64-67.
[13]
王怡茹1 韦婧2 刘萍1▲. 冠心病斑块炎症反应与中医阴阳相关性的探讨 [J]. 中国医药导报, 2020, 17(32): 128-130.
[14]
欧阳夏荔1 段浩茹1 金琪2 赵百孝3 韩丽3 罗雪3 赵思雨3 张高钰3 张杨旖旎3 程元元3. 保健灸关元穴对老年大鼠血清和肠道氧化及炎症反应的影响 [J]. 中国医药导报, 2020, 17(31): 12-15,29.
[15]
张林丽1 宋景贵2. CD4 T淋巴细胞在脑卒中后抑郁发病机制中的研究进展 [J]. 中国医药导报, 2020, 17(31): 62-65.