Dexras1介导的炎症反应在蛛网膜下腔出血后白质损伤中的作用

辛元君; 黄豪; 梁译丹; 覃王; 吴欣桐; 罗雪峰; 梁芙铭; 何朝晖

doi:10.16016/j.1000-5404.202002207

您当前的位置：

首页 >

文章列表页 >

Dexras1介导的炎症反应在蛛网膜下腔出血后白质损伤中的作用

基础医学 | 更新时间：2026-01-09

- Dexras1介导的炎症反应在蛛网膜下腔出血后白质损伤中的作用
- Role of Dexras1-mediated inflammatory response in white matter damage after subarachnoid hemorrhage in rats
- 第三军医大学学报 2020年42卷第13期页码：1315-1322
- 作者机构：
  
  400016 重庆, 重庆医科大学附属第一医院神经外科
- 作者简介：
  
  [ 何朝晖, E-mail:hezhaohui@hospital.cqmu.edu.cn HE Zhaohui, E-mail:hezhaohui@hospital.cqmu.edu.cn
- 基金信息：
  
  ‍基‍金‍项‍目‍］‍ ‍国家自然科学基金面上项目(81870927);重庆市自然科学基金面上项目(CSTC2019jcyj-msxmX0239)
- DOI：10.16016/j.1000-5404.202002207
  中图分类号： R363.21;R741.02;R743.35
- 收稿：2020-02-27，
  
  修回：2020-03-13，
  
  纸质出版：2020-07-15
- 稿件说明：
移动端阅览
辛元君, 黄豪, 梁译丹, 等. Dexras1介导的炎症反应在蛛网膜下腔出血后白质损伤中的作用[J]. 第三军医大学学报, 2020,42(13):1315-1322.

Yuanjun XIN, Hao HUANG, Yidan LIANG, et al. Role of Dexras1-mediated inflammatory response in white matter damage after subarachnoid hemorrhage in rats[J]. Journal of Third Military Medical University, 2020, 42(13): 1315-1322.
辛元君, 黄豪, 梁译丹, 等. Dexras1介导的炎症反应在蛛网膜下腔出血后白质损伤中的作用[J]. 第三军医大学学报, 2020,42(13):1315-1322. DOI： 10.16016/j.1000-5404.202002207.

Yuanjun XIN, Hao HUANG, Yidan LIANG, et al. Role of Dexras1-mediated inflammatory response in white matter damage after subarachnoid hemorrhage in rats[J]. Journal of Third Military Medical University, 2020, 42(13): 1315-1322. DOI： 10.16016/j.1000-5404.202002207.

摘要

目的

探索Dexras1在蛛网膜下腔出血(subarachnoid hemorrhage

SAH)中促进炎症和参与白质损伤(white matter damage

WMD)的机制。

方法

将90只成年健康雄性SD大鼠作为研究对象

采用随机抽签的形式将其分为假手术sham组、SAH组、SAH时间点组、SAH+LV-Scramble组、SAH+LV-Dexras1

组和SAH+LV-Dexras1

组

每组12只

利用血管内穿刺法构建大鼠在体蛛网膜下腔出血模型

免疫荧光及神经脊髓固蓝染色分别观察各组皮层髓鞘变化

神经行为学评分检测神经功能变化情况；Western blot检测各组Dexras1、TNF-α、IL-1β及MBP的表达。

结果

与sham组比较

SAH后大鼠脑组织中Dexras1、TNF-α、IL-1β明显升高(

0.01)

MBP明显减少(

0.01)

出现明显的神经功能缺损、脑水肿、髓鞘损伤及炎症细胞浸润；与SAH+LV-Scramble组比较

SAH+LV-Dexras1

组大鼠脑组织中Dexras1、TNF-α、IL-1β继续升高(

0.01)

MBP进一步降低(

0.05)

神经功能缺损、脑水肿、髓鞘损伤明显加重

炎症细胞浸润也显著增多；而SAH+LV-Dexras1

组大鼠脑组织中Dexras1、TNF-α、IL-1β明显降低(

0.01)

MBP升高(

0.05)

神经功能缺损、脑水肿、髓鞘损伤明显改善

炎症细胞浸润也显著减少。

结论

Dexras1在蛛网膜下腔出血中具有促进炎症反应

从而参与蛛网膜下腔出血后白质损伤的作用。

Abstract

Objective

To explore the mechanisms by which Dexras1 promotes inflammation and participates in white matter damage (WMD) after subarachnoid hemorrhage (SAH).

Methods

Ninety healthy adult male SD rats were randomly divided into control group (sham group)

SAH group

SAH time ponits group

SAH+LV-Scramble group

SAH+LV-Dexras1+ group

and SAH+LV-Dexras1

group

with 12 rats in each group. Intravascular puncture was used to establish a rat model of intracranial hemorrhage under subarachnoid. Immunofluorescence assay and Luxol fast blue staining were used to detect myelin changes in each group; Neurobehavioral scores were used to evaluate the changes in neurological function; Western blot analysis was used to detect the expression of Dexras1

TNF-α

IL-1β and myelin basic protein (MBP) in each group.

Results

Compared with the sham group

Dexras1

TNF-α

and IL-1β were significantly increased in the brain tissue (

0.01)

MBP was significantly reduced (

0.01)

and obvious neurological deficits

cerebral edema

myelin sheath injury and inflammatory cell infiltration were observed in the SAH group. Compared with the SAH+LV-Scramble group

Dexras1

TNF-α

and IL-1β in the brain tissue of the SAH+LV-Dexras1+ group continued to increase (

0.01)

MBP was further reduced (

0.05)

and neurological deficits

cerebral edema

and myelin sheath damage were significantly aggravated

and inflammatory cell infiltration was also significantly increased in the group. However

Dexras1

TNF-α

and IL-1β in the brain tissue were significantly reduced (

0.01)

MBP was increased (

0.05)

and neurological deficits

cerebral edema and myelin sheath damage were obviously improved

inflammatory cell infiltration was significantly reduced in the SAH+LV-Dexras1

group.

Conclusion

Dexras1 can promote the inflammatory response

and thereby participate in white matter damage after SAH.

关键词

Keywords

references

MACDONALD R L, SCHWEIZER T A. Spontaneous subarachnoid haemorrhage[J]. Lancet, 2017, 389(10069): 655-666. DOI:10.1016/s0140-6736(16)30668-7.

LI R, VENKAT P, CHOPP M, et al . RP001 hydrochloride improves neurological outcome after subarachnoid hemorrhage[J ] . J Neurol Sci, 2019, 399: 6-14. DOI:10.1016/j.jns.2019.02.005.

STEPHENSON J, NUTMA E, VAN DER VALK P, et al . Inflammation in CNS neurodegenerative diseases[J ] . Immunology, 2018, 154(2): 204-219. DOI:10.1111/imm.12922.

BEVERS M B, WOLCOTT Z, BACHE S, et al . Soluble ST2 links inflammation to outcome after subarachnoid hemorrhage[J ] . Ann Neurol, 2019, 86(3): 384-394. DOI:10.1002/ana.25545.

LUCKE-WOLD B P, LOGSDON A F, MANORANJAN B, et al . Aneurysmal subarachnoid hemorrhage and neuroinflammation: a comprehensive review[J ] . Int J Mol Sci, 2016, 17(4): 497. DOI:10.3390/ijms17040497.

CHENG H Y, OBRIETAN K. Dexras1: shaping the responsiveness of the circadian clock[J]. Semin Cell Dev Biol, 2006, 17(3): 345-351. DOI:10.1016/j.semcdb.2006.03.006.

THAPLIYAL A, VERMA R, KUMAR N. Small G proteins Dexras1 and RHES and their role in pathophysiological processes[J]. Int J Cell Biol, 2014, 2014: 308535. DOI:10.1155/2014/308535.

GREENWOOD M P, GREENWOOD M, MECAWI A S, et al . Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation[J ] . Mol Brain, 2 016, 9: 1. DOI:10.1186/s13041-015-0182-2.

GRAHAM T E, QIAO Z, DORIN R I. Dexras1 inhibits adenylyl cyclase[J]. Biochem Biophys Res Commun, 2004, 316(2): 307-312. DOI:10.1016/j.bbrc.2004.02.049.

ONG S A, TAN J J, TEW W L, et al . Rasd1 modulates the coactivator function of NonO in the cyclic AMP pathway[J ] . PLoS ONE, 2011, 6(9): e24401. DOI:10.1371/journal.pone.0024401.

MO J, ENKHJARGAL B, TRAVIS Z D, et al . AVE 0991 attenuates oxidative stress and neuronal apoptosis via Mas/PKA/CREB/UCP-2 pathway after subarachnoid hemorrhage in rats[J ] . Redox Biol, 2019, 20: 75-86. DOI:10.1016/j.redox.2018.09.022.

CHEN J Y, QIAN C, DUAN H Y, et al . Melatonin attenuates neurogenic pulmonary edema via the regulation of inflammation and apoptosis after subarachnoid hemorrhage in rats[J ] . J Pineal Res, 2015, 59(4): 469-477. DOI:10.1111/jpi.12278.

GERAERTS M, EGGERMONT K, HERNANDEZ-ACOSTA P, et al . Lentiviral vectors mediate efficient and stable gene transfer in adult neural stem cells in vivo [J ] . Hum Gene Ther, 2006, 17(6): 635-650. DOI:10.1089/hum.2006.1 7.635..

XU H B, QIN W Y, HU X, et al . Lentivirus-mediated overexpression of OTULIN ameliorates microglia activation and neuroinflammation by depressing the activation of the NF-κB signaling pathway in cerebral ischemia/reperfusion rats[J ] . J Neuroinflam, 2018, 15(1): 83. DOI:10.1186/s12974-018-1117-5.

ZHOU K R, ENKHJARGAL B, XIE Z Y, et al . Dihydrolipoic acid inhibits lysosomal rupture and NLRP3 through lysosome-associated membrane protein-1/calcium/calmodulin-dependent protein kinase II/TAK1 pathways after subarachnoid hemorrhage in rat[J ] . Stroke, 2018, 49(1): 175-183. DOI:10.1161/STROKEAHA.117.018593.

TAKAHASHI E, DAI G P, ROSEN G D, et al . Developing neocortex organization and connectivity in cats revealed by direct correlation of diffusion tractography and histology[J ] . Cereb Cortex, 2011, 21(1): 200-211. DOI:10.1093/cercor/bhq084.

YEO S S, CHOI B Y, CHANG C H, et al . Evidence of corticospinaltract injury at midbrain in patients with subarachnoid hemorrhage[J ] . Stroke, 2012, 43(8): 2239-2241. DOI:10.1161/STROKEAHA.112.661116.

EGASHIRA Y, HUA Y , KEEP R F, et al . Acute white matter injury after experimental subarachnoid hemorrhage: potential role of lipocalin 2[J ] . Stroke, 2014, 45(7): 2141-2143. DOI:10.1161/STROKEAHA.114.005307.

ZANNO A E, ROMER M A, FOX L, et al . Reducing Th2 inflammation through neutralizing IL-4 antibody rescues myelination in IUGR rat brain[J ] . J Neurodev Disord, 2019, 11(1): 34. DOI:10.1186/s11689-019-9297-6.

LEONETTI C, MACREZ R, PRUVOST M, et al . Tissue-type plasminogen activator exerts EGF-like chemokinetic effects on oligodendrocytes in white matter(re)myelination[J ] . Mol Neurodegener, 2017, 12(1): 20. DOI:10.1186/s13024-017-0160-5.

WIXEY J A, LEE K M, MILLER S M, et al . Neuropathology in intrauterine growth restricted newborn piglets is associated with glial activation and proinflammatory status in the brain[J ] . J Neuroinflammation, 2019, 16(1): 5. DOI:10.1186/s12974-018-1392-1.

KUMMER T T, MAGNONI S, MACDONALD C L, et al . Experimental subarachnoid haemorrhage results in multifocal axonal injury[J ] . Brain, 2015, 138(Pt 9): 2608-2618. DOI:10.1093/brain/awv180.

BOUCHARD-CANNON P, LOWDEN C, TRINH D, et al . Dexras1 is a homeostatic regulator of exercise-dependent proliferation and cell survival in the hippocampal neurogenic niche[J ] . Sci Rep, 2018, 8(1): 5294. DOI:10.1038/s41598-018-23673-z.

KHAN R S, BAUMANN B, DINE K, et al . Dexras1 deletion and iron chelation promote neuroprotection in experimental optic neuritis[J ] . Sci Rep, 2019, 9(1): 11664. DOI:10.1038/s41598-019-48087-3.

ZHAO Q, CHE X D, ZHANG H X, et al . Thioredoxin-interacting protein links endoplasmic Reticulum stress to inflammatory brain injury and apoptosis after subarachnoid haemorrhage[J ] . J Neuroinflammation, 2017, 14(1): 104. DOI:10.1186/s12974-017-0878-6.

ZHAO Y S, WANG H Y, CHEN W, et al . Melatonin attenuates white matter damage after focal brain ischemia in rats by regulating the TLR4/NF-κB pathway[J ] . Brain Res Bull, 2019, 150: 168-178. DOI:10.1016/j.brainresbull.2019.05.019.

OKADA T, SUZUKI H. Mechanisms of neuroinflammation and inflammatory mediators involved in brain injury following subarachnoid hemorrhage[J]. Histol Histopathol, 2020: 18208. DOI:10.14670/HH-18-208.

ZHUANG K, ZUO Y C, SHERCHAN P, et al . Hydrogen inhalation attenuates oxidative stress related endothelial cells injury after subarachnoid hemorrhage in rats[J ] . Front Neurosci, 2019, 13: 1441. DOI:10.3389/fnins.2019.01441.

SONG S S, WANG S X, PIGOTT V M, et al . Selective role of Na + /H + exchanger in Cx3cr1 + microglial activation, white matter demyelination, and post-stroke function recovery[J ] . Glia, 2018, 66(11): 2279-2298. DOI:10.1002/glia.23456..

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

动脉瘤性蛛网膜下腔出血后迟发性脑缺血早期识别：一项多因素临床预测模型的建立与验证

MAVS功能丧失性突变导致抗病毒免疫缺陷：揭示病毒感染触发儿童泛发性脓疱性银屑病的新机制

Z-藁本内酯通过抑制PI3K/AKT信号通路延缓视网膜色素变性：基于网络药理学与分子对接验证

ATF3通过抑制ATG5和ATG16L1表达调控巨噬细胞自噬与炎症反应

新型吩噻嗪衍生物DA414在大鼠脑出血中的作用及机制研究