低分子肝素通过促进SUMO2/3蛋白的表达及核转移对脑缺血再灌注大鼠发挥脑保护作用

顾小飞; 李恒; 杨桐榉; 王凯; 王丽君; 王震; 陈力勇

doi:10.16016/j.1000-5404.201701065

您当前的位置：

首页 >

文章列表页 >

低分子肝素通过促进SUMO2/3蛋白的表达及核转移对脑缺血再灌注大鼠发挥脑保护作用

基础医学 | 更新时间：2026-01-09

- 低分子肝素通过促进SUMO2/3蛋白的表达及核转移对脑缺血再灌注大鼠发挥脑保护作用
- Low molecular heparins exert brain protective effect in MCAO rats by promoting nuclear transfer and SUMO2/3 expression
- 第三军医大学学报 2017年39卷第11期页码：1123-1129
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201701065
  中图分类号：
- 收稿：2017-01-11，
  
  纸质出版：2017-06-15
- 稿件说明：
移动端阅览
顾小飞, 李恒, 杨桐榉, 等. 低分子肝素通过促进SUMO2/3蛋白的表达及核转移对脑缺血再灌注大鼠发挥脑保护作用[J]. 第三军医大学学报, 2017,39(11):1123-1129.

Xiaofei Gu, Heng Li, Tongju Yang, et al. Low molecular heparins exert brain protective effect in MCAO rats by promoting nuclear transfer and SUMO2/3 expression[J]. Journal of Third Military Medical University, 2017, 39(11): 1123-1129.
顾小飞, 李恒, 杨桐榉, 等. 低分子肝素通过促进SUMO2/3蛋白的表达及核转移对脑缺血再灌注大鼠发挥脑保护作用[J]. 第三军医大学学报, 2017,39(11):1123-1129. DOI： 10.16016/j.1000-5404.201701065.

Xiaofei Gu, Heng Li, Tongju Yang, et al. Low molecular heparins exert brain protective effect in MCAO rats by promoting nuclear transfer and SUMO2/3 expression[J]. Journal of Third Military Medical University, 2017, 39(11): 1123-1129. DOI： 10.16016/j.1000-5404.201701065.

摘要

Abstract

Objective

To determine the effect of low molecular weight heparins (LMWH) on NF-κB activation and expression after cerebral ischemia-reperfusion injury (CIRI) in rats and investigate the possible mechanism.

Methods

Middle cerebral artery occlusion (MCAO) model was established by Longa's method in rats. Then the rats were assigned into 3 groups

that is

sham operation group (Sham

=20)

ischemia reperfusion group (I/R

=20)

LMWH intervention group (LMWH

1.5 mg/kg

intravenous injection

5 min prior to reperfusion

=20). After neurological function was evaluated

the rats were sacrificed in 3 and 24 h after reperfusion

and the brain tissues were harvested for infarct volume. Western blotting

immunohistochemical (IHC) and immunofluorescence (IF) assay were used to detect the expression levels of IL-1β

NF-κB P65 and small ubiquitin-related modifier 2/3 (SUMO2/3).

Results

① Neurological function evaluation showed that MCAO resulted in severe neurological dysfunction in the rats

but LMWH intervention obviously attenuated the injury (

0.01). ② Cerebral I/R injury induced severe cerebral infarction (

0.01)

but

LMWH alleviated the symptoms (

0.01)

and the effects were more significant in the striatum region that was sensitive to infarction (

0.01). ③ Western blot results showed that the protein levels of IL-1β and NF-κB P65 were significantly higher in I/R group than sham operation group in 24 h after reperfusion (

0.01)

while LMWH intervention obviously attenuated the levels. In 3 h after reperfusion

SUMO2/3 protein level was higher in the I/R group than the sham operation group (

0.01). But interestingly

LMWH intervention increased the expression level significantly (

0.01). ④ IHC and IF results showed that after 3 hours' reperfusion

SUMO2/3 protein level was higher in the I/R group than the sham operation group

and nuclear transfer phenomeno

n appeared

mainly occurred in the neurons (

0.01). After LMWH intervention

there were significantly more neurons with SUMO2/3 protein nuclear transfer (

0.01).

Conclusion

LMWH can promote the SUMO2/3 protein level and increase nuclear transfer in rats after CIRI

and then possibly influence the NF-κB activation and reduce the production of inflammatory factors.

关键词

Keywords

references

Quartermain D Li Y S Jonas S The low molecular weight heparin enoxaparin reduces infarct size in a rat model of temporary focal ischemia Cerebrovasc Dis 2003 16 4 346 355 10.1159/000072556 Quartermain D, Li Y S, Jonas S. The low molecular weight heparin enoxaparin reduces infarct size in a rat model of temporary focal ischemia[J]. Cerebrovasc Dis, 2003, 16(4): 346-355. DOI: 10.1159/000072556.

Stutzmann J M Mary V Wahl F Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo models of cerebral ischemia or traumatic brain injury in rats: a review CNS Drug Rev 2002 8 1 1 30 10.1111/j.1527-3458.2002.tb00213.x Stutzmann J M, Mary V, Wahl F, et al . Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo models of cerebral ischemia or traumatic brain injury in rats: a review[J ] . CNS Drug Rev, 2002, 8(1): 1-30. DOI:10.1111/j.1527-3458.2002.tb00213.x.

Stephenson D Yin T Smalstig E B Transcription factor nuclear factor-kappa B is activated in neurons after focal cerebral ischemia J Cereb Blood Flow Metab 2000 20 3 592 603 10.1097/00004647-200003000-00017 Stephenson D, Yin T, Smalstig E B, et al . Transcription factor nuclear factor-kappa B is activated in neurons after focal cerebral ischemia[J ] . J Cereb Blood Flow Metab, 2000, 20(3): 592-603. DOI:10.1097/00004647-200003000-00017.

Zhao D Ding R Mao Y Heparin rescues sepsis-associated acute lung injury and lethality through the suppression of inflammatory responses Inflammation 2012 35 6 1825 1832 10.1007/s10753-012-9503-0 Zhao D, Ding R, Mao Y, et al . Heparin rescues sepsis-associated acute lung injury and lethality through the suppression of inflammatory responses[J ] . Inflammation, 2012, 35(6): 1825-1832. DOI:10.1007/s10753-012-9503-0.

Li X Zheng Z Li X Unfractionated heparin inhibits lipopolysaccharide-induced inflammatory response through blocking p38 MAPK and NF-κB activation on endothelial cell Cytokine 2012 60 1 114 121 10.1016/j.cyto.2012.06.008 Li X, Zheng Z, Li X, et al . Unfractionated heparin inhibits lipopolysaccharide-induced inflammatory response through blocking p38 MAPK and NF-κB activation on endothelial cell[J ] . Cytokine, 2012, 60(1): 114-121. DOI:10.1016/j.cyto.2012.06.008.

Lee Y J Hallenbeck J M SUMO and ischemic tolerance Neuromolecular Med 2013 15 4 771 781 10.1007/s12017-013-8239-9 Lee Y J, Hallenbeck J M. SUMO and ischemic tolerance[J]. Neuromolecular Med, 2013, 15(4): 771-781. DOI:10.1007/s12017-013-8239-9.

Aillet F Lopitz-Otsoa F Egaña I Heterologous SUMO-2/3-ubiquitin chains optimize IκBα degradation and NF-κB activity PLoS ONE 2012 7 12 e51672 10.1371/journal.pone.0051672 Aillet F, Lopitz-Otsoa F, Egaña I, et al . Heterologous SUMO-2/3-ubiquitin chains optimize IκBα degradation and NF-κB activity[J ] . PLoS ONE, 2012, 7(12): e51672. DOI:10.1371/journal.pone.0051672.

Huang W Xu L Zhou X High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells Biochem Biophys Res Commun 2013 438 3 568 574 10.1016/j.bbrc.2013.07.065 Huang W, Xu L, Zhou X, et al . High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells[J ] . Biochem Biophys Res Commun, 2013, 438(3): 568-574. DOI:10.1016/j.bbrc.2013.07.065.

Garcia J H Wagner S Liu K F Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation Stroke 1995 26 4 627 634 10.1161/01.str.26.4.627 Garcia J H, Wagner S, Liu K F, et al . Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation[J ] . Stroke, 1995, 26(4): 627-634. DOI:10.1161/01.str.26.4.627.

Datwyler A L Lättig-Tünnemann G Yang W SUMO2/3 conjugation is an endogenous neuroprotective mechanism J Cereb Blood Flow Metab 2011 31 11 2152 2159 10.1038/jcbfm.2011.112 Datwyler A L, Lättig-Tünnemann G, Yang W, et al . SUMO2/3 conjugation is an endogenous neuroprotective mechanism[J ] . J Cereb Blood Flow Metab, 2011, 31(11): 2152-2159. DOI:10.1038/jcbfm.2011.112.

Wang L Ma Q Yang W Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons J Neurochem 2012 123 3 349 359 10.1111/j.1471-4159.2012.07916.x Wang L, Ma Q, Yang W, et al . Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons[J ] . J Neurochem, 2012, 123(3): 349-359. DOI:10.1111/j.1471-4159.2012.07916.x.

Iwabuchi M Sheng H Thompson J W Characterization of the ubiquitin-modified proteome regulated by transient forebrain ischemia J Cereb Blood Flow Metab 2014 34 3 425 432 10.1038/jcbfm.2013.210 Iwabuchi M, Sheng H, Thompson J W, et al . Characterization of the ubiquitin-modified proteome regulated by transient forebrain ischemia[J ] . J Cereb Blood Flow Metab, 2014, 34(3): 425-432. DOI:10.1038/jcbfm.2013.210.

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

利拉鲁肽通过NOX2调控小胶质细胞/巨噬细胞极化改善糖尿病大鼠脑缺血损伤

敲除Vanin-1促进肾缺血再灌注损伤后功能恢复的作用及机制

干细胞因子联合抗白细胞介素17A抗体对小鼠脑缺血预后的影响

NF-κB抑制剂对脂多糖刺激的退变人椎间盘髓核细胞炎症因子表达的影响