[1]石计朋,宋亚辉,栗延伟,等.ω-3多不饱和脂肪酸对脂多糖诱导的脑损伤新生大鼠的神经保护作用[J].新乡医学院学报,2018,35(5):368-372.[doi:10.7683/xxyxyxb.2018.05.003]
　SHI Ji-peng,SONG Ya-hui,LI Yan-wei,et al.Neuroprotective effect of ω-3 polyunsaturated fatty acid on brain injury induced by lipopolysaccharide in neonatal rats[J].Journal of Xinxiang Medical University,2018,35(5):368-372.[doi:10.7683/xxyxyxb.2018.05.003]
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ω-3多不饱和脂肪酸对脂多糖诱导的脑损伤新生大鼠的神经保护作用
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
35
期数:
2018年5
页码:
368-372
栏目:
基础研究
出版日期:
2018-05-05

文章信息/Info

Title:
Neuroprotective effect of ω-3 polyunsaturated fatty acid on brain injury induced by lipopolysaccharide in neonatal rats
作者:
石计朋1; 宋亚辉2; 栗延伟3; 郭喜霞1; 李树军4; 尚云1; 桑桂梅1; 高俊1; 郭洪旭1; 王卫卫1; 李珍珍1; 唐成和1; 黄丽密5
（1.新乡医学院第一附属医院新生儿科，河南　卫辉　453100；2.南阳市第二人民医院超声科，河南　南阳　473000；3.新乡医学院第三附属医院神经内科，河南　新乡　453003；4.新乡医学院第一附属医院儿童重症监护病房，河南　卫辉　453100；5.温州医科大学附属第一医院新生儿科，浙江　温州　325000）
Author(s):
SHI Ji-peng1; SONG Ya-hui2; LI Yan-wei3; GUO Xi-xia1; LI Shu-jun4; SHANG Yun1; SANG Gui-mei1; GAO Jun1; GUO Hong-xu1; WANG Wei-wei1; LI Zhen-zhen1; TANG Cheng-he1; HUANG Li-mi5
（1.Department of Neonatology，the First Affiliated Hospital of Xinxiang Medical University，Weihui；2.Department of Ultrasonography Lab，the Second People′s Hospital of Nanyang City，Nanyang；3.Department of Neurology，the Third Affiliated Hospital of Xinxiang Medical University，Xinxiang；4.Department of Pediatric Intensive Care Unit，the First Affiliated Hospital of Xinxiang Medical University，Weihui；5.Department of Neonatology，the First Affiliated Hospital of Wenzhou Medical University，Wenzhou）
关键词:
脂肪乳; ω-3多不饱和脂肪酸; 脑损伤; 脂多糖; Toll样受体4; 核因子-κB; 肿瘤坏死因子-α; 白细胞介素-1β; 白细胞介素-6
Keywords:
fat emulsion; ω-3 polyunsaturated fatty acid; brain injury; lipopolysaccharide; Toll like receptor 4; nuclear factor-κB; tumor necrosis factor-α; interleukin-1β; interleukin-6
分类号:
R651
DOI:
10.7683/xxyxyxb.2018.05.003
文献标志码:
A
摘要:
目的　探讨ω-3多不饱和脂肪酸（ω-3 PUFA）对脂多糖（LPS）诱导的脑损伤新生大鼠的神经保护作用。方法　将48只3日龄Sprague-Dawley新生大鼠随机分为对照组、LPS组、ω-3 PUFA组和ω-6 PUFA组，每组12只。LPS组、ω-3 PUFA组和 ω-6 PUFA组大鼠腹腔注射0.6 mg·kg-1 LPS建立脑损伤模型，然后分别立即腹腔注射等容积的生理盐水、ω-3 PUFA和 ω-6 PUFA；对照组大鼠腹腔注射等容积的生理盐水。24 h后处死各组大鼠，取海马组织，采用实时荧光定量聚合酶链反应和Western blot法检测各组大鼠海马组织中Toll样受体4（TLR4）、核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6的mRNA和蛋白表达。结果　LPS组、ω-3 PUFA组、ω-6 PUFA组新生大鼠海马组织中TLR4、NF-κB、TNF-α、IL-1β及IL-6 mRNA和蛋白表达均高于对照组（P<0.05）；ω-6 PUFA组新生大鼠海马组织中TLR4、NF-κB、TNF-α、IL-1β及IL-6 mRNA和蛋白表达高于LPS组（P<0.05）；ω-3 PUFA组新生大鼠海马组织中TLR4、NF-κB、TNF-α、IL-1β及IL-6 mRNA和蛋白表达均低于LPS组和ω-6 PUFA组（P<0.05）。结论　ω-3 PUFA能下调大鼠海马组织中TLR4/NF-κB信号通路，减少炎性因子TNF-α、IL-1β、IL-6释放，对LPS所致的脑损伤新生大鼠有神经保护作用。
Abstract:
Objective　To investigate neuroprotective effect of ω-3 polyunsaturated fatty acid（ω-3 PUFA) on brain injury induced by lipopolysaccharide（LPS） in neonatal rats.Methods　Forty-eight neonatal Sprague-Dawley rats（3 days）were randomly divided into control group，LPS group，ω-3 PUFA group and ω-6 PUFA group，with 12 rats in each group.The rats in the LPS group，ω-3 PUFA group and ω-6 PUFA group were given 0.6 mg·kg-1 LPS via intraperitoneal injection to establish the brain inury model，then equal volume of saline，ω-3 PUFA and ω-6 PUFA was immediately given via intraperitoneal injection respectively；while the rats in the control group were given equal volume of saline.Those rats were sacrificed after 24 hours.The expression of Toll like receptor 4（TLR4），nuclear factor-κB（NF-κB），tumor necrosis factor-α（TNF-α），interleukin （IL）-1β and IL-6 mRNA in hippocampus was examined by real-time quantitative polymerase chain reaction，meanwhile the expression of TLR4，NF-κB，TNF-α，IL-1β and IL-6 protein in hippocampus was measured by Western blot.Results　The expression of TLR4，NF-κB，TNF-α，IL-1β,IL-6 mRNA and protein in rats hippocampus in the LPS group，ω-3 PUFA group and ω-6 PUFA group was significantly higher than that in the control group（P<0.05）.The expression of TLR4，NF-κB，TNF-α，IL-1β,IL-6 mRNA and protein in rats hippocampus in the ω-6 PUFA group was significantly higher than that in the LPS group（P<0.05）.The expression of TLR4，NF-κB，TNF-α，IL-1β,IL-6 mRNA and protein in rats hippocampus in the ω-3 PUFA group was significantly lower than that in the LPS group and ω-6 PUFA group（P<0.05）.Conclusion　ω-3 PUFA can play a role of neuroprotective effect on brain injury induced by LPS in neonatal rats.The mechanism may involve in down-regulate the activity of TLR4 and NF-κB and reduce the release of TNF-α，IL-1β and IL-6.

参考文献/References:

［1］　VOLPE J J.Encephalopathy of prematurity includes neuronal abnormalities［J］.Pediatrics，2005，116（1）：221-225.
［2］　GROENENDAAL F，TERMOTE U，VAN DER HEIDE-JALVING M，et al.Complications affecting preterm neonates from 1991 to 2006：what have we gained［J］.Acta Paediatrica，2010，99（3）：354-358.
［3］　DEAN J M，SHI Z，FLEISS B，et al.A critical review of models of perinatal infection［J］.Dev Neurosci，2015，37（4/5）：289-304.
［4］　HUSCHAK G，ZUR N K，HOELL T，et al.Olive oil based nutrition in multiple trauma patients：a pilot study［J］.Intensive Care Med，2005，31（9）：1202-1208.
［5］　石计朋，闫建国，韩金芬，等.ω-3 PUFAs对LPS诱导急性肺损伤大鼠前炎症因子TNF-α、IL-1β、IL-6的影响［J］.中国儿童保健杂志，2014，22（1）：35-37，40.
［6］　石计朋，黄丽密，钱燕，等.脂肪乳剂对脂多糖诱导的急性肺损伤中细胞因子IL-1β和IL-6的影响［J］.临床儿科杂志，2014，32（3）：250-253.
［7］　黄丽密，石计朋，余震，等.脂肪乳剂对急性肺损伤大鼠肺组织病理形态的影响［J］.肠外与肠内营养，2012，19（2）：107-110.
［8］　GRAHAM E M，HOLCROFT C J，RAI K K，et al.Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis［J］.Am J Obstet Gynecol，2004，191（4）：1305-1310.
［9］　齐可民，樊超男.n-3多不饱和脂肪酸与儿童生长发育和健康［J］.中华实用儿科临床杂志，2016，31（23）：1761-1765.
［10］　WILLIAMS J J，MAYURASAKORN K，VANNUCCI S J，et al.N-3 fatty acid rich triglyceride emulsions are neuroprotective after cerebral hypoxic-ischemic injury in neonatal mice［J］.PLoS One，2013，8（2）：e56233.
［11］　STOLL B J，HANSEN N I，ADAMS-CHAPMAN I，et al.Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection［J］.JAMA，2004，292（19）：2357-2365.
［12］　FAN L W，TIEN L T，ZHENG B，et al.Dopaminergic neuronal injury in the adult rat brain following neonatal exposure to lipopolysaccharide and the silent neurotoxicity［J］.Brain Behav Immun，2011，25（2）：286-297.
［13］　CHAU V，BRANT R，POSKITT K J，et al.Postnatal infection is associated with widespread abnormalities of brain development in premature newborns［J］.Pediatr Res，2012，71（3）：274-279.
［14］　BIRAN V，VERNEY C，FERRIERO D M.Perinatal cerebellar injury in human and animal models［J］.Neurol Res Int，2012，2012：858929.
［15］　孙园园，郭大东，陈美清，等.rno-miR-30b-5p在葡萄膜炎发病过程中对白细胞介素-10和Toll样受体4表达的调控作用［J］.眼科新进展，2017，37（4）：330-334.
［16］　武宇辉，齐颖，马伟科，等.微小RNA-155和微小RNA-21对脓毒症患儿Toll样受体4表达的影响［J］.中华实用儿科临床杂志，2017，32（6）：420-424.
［17］　张经，肖青，姜发纲，等.Toll样受体4对2型糖尿病小鼠视网膜病变的影响［J］.眼科新进展，2016，36（9）：805-808.
［18］　丁国龙，谢安明，雷剑琴，等.增生型糖尿病视网膜病变患者玻璃体内注射贝伐单抗后房水中细胞因子的变化及其相关性分析［J］.眼科新进展，2017，37（4）：358-361.
［19］　YAO L，KAN E M，LU J，et al.Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia：role of TLR4 in hypoxic microglia［J］.J Neuroinflammation，2013，10：23.
［20］　YANG S，LI R，QU X，et al.Fosinoprilat alleviates lipopolysaccharide （LPS）-induced inflammation by inhibiting TLR4/NF-kappa B signaling in monocytes［J］.Cell Immunol，2013，284（1/2）：182-186.
［21］　GORINA R，FONT-NIEVES M，MARQUEZ-KISINOUSKY L，et al.Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NF kappa B signaling，MAPK，and Jak1/Stat1 pathways［J］.Glia，2011，59（2）：242-255.
［22］　KAUR C，RATHNASAMY G，LING E A.Roles of activated microglia in hypoxia induced neuroinflammation in the developing brain and the retina［J］.J Neuroimmune Pharmacol，2013，8（1）：66-78.
［23］　FAN L W，TIEN L T，ZHENG B，et al.Interleukin-1beta-induced brain injury and neurobehavioral dysfunctions in juvenile rats can be attenuated by alpha-phenyl-n-tert-butyl-nitrone［J］.Neuroscience，2010，168（1）：240-252.
［24］　宋亚辉，尤庆旺，王倩楠，等.Omega-3鱼油脂肪乳对缺氧缺血性脑损伤新生大鼠海马组织Toll样受体4和核因子κB的影响［J］.中华实用儿科临床杂志，2016，31（12）：923-926.
［25］　程力平，张群威，高小玲，等.血清Toll样受体4和肿瘤坏死因子-α水平与早产儿脑损伤的关系［J］.新乡医学院学报，2017，34 （1）：50-52.

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更新日期/Last Update: 2022-03-16