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:
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.
Low molecular heparins exert brain protective effect in MCAO rats by promoting nuclear transfer and SUMO2/3 expression
摘要
Abstract
Objective
2
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
2
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
n
=20)
ischemia reperfusion group (I/R
n
=20)
LMWH intervention group (LMWH
1.5 mg/kg
intravenous injection
5 min prior to reperfusion
n
=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
2
① Neurological function evaluation showed that MCAO resulted in severe neurological dysfunction in the rats
but LMWH intervention obviously attenuated the injury (
P
<
0.01). ② Cerebral I/R injury induced severe cerebral infarction (
P
<
0.01)
but
LMWH alleviated the symptoms (
P
<
0.01)
and the effects were more significant in the striatum region that was sensitive to infarction (
P
<
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 (
P
<
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 (
P
<
0.01). But interestingly
LMWH intervention increased the expression level significantly (
P
<
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 (
P
<
0.01). After LMWH intervention
there were significantly more neurons with SUMO2/3 protein nuclear transfer (
P
<
0.01).
Conclusion
2
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
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