Effects of bone marrow mononuclear cells transplantation on ERK1/2 signal pathway after cerebral infarction in rats
10.3760/cma.j.issn.1674-6554.2017.08.002
- VernacularTitle:骨髓单个核细胞移植对脑梗死大鼠ERK1/2信号通路的影响
- Author:
Ningning CHEN
;
Jianping WANG
;
Xiaojie FU
;
Hengfang LIU
;
Min ZHANG
;
Yuanzheng ZHAO
- Keywords:
Bone marrow mononuclear cells (BMMNCs);
Cerebral infarction;
Neuroprotection;
ERK1/2 signaling pathway
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2017;26(8):678-683
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the neuroprotection and mechanisms of bone marrow mononuclear cells (BMMNCs),and evaluate whether ERK1/2 signaling pathway was involved in it.Methods384 healthy male SD rats,which were 6-8 week old,weighting 250-280 g,were selected.The middle cerebral artery occlusion (MCAO) model was established in SD rats using the suture method.The rats were randomly divided into sham operation group,model group,BMMNCs group and ERK1/2 inhibitor group,with 96 rats in each group.At the time of 24 h after the successful modeling,200 μl PBS solution was injected into the caudal vein of the rats in the model group,200 μl PBS solution containing 5×106 BMMNCs was injected into the rats in the BMMNCs group and the ERK1/2 inhibitor group.meanwhile,5 μl PD98059 was injected into the lateral ventricle of the brain of rats in the ERK1/2 inhibitor group.At the time points of 3 d,7 d and 14 d,the modified neurological severity scores (mNSS) was used to evaluate the neurological function,the volume of cerebral infarction was assessed by TTC staining,the pERK1/2,Bax,Bcl-2 and caspase-3 levels were detected by Western blot,and the effect of BMMNCs on activation of microglia was detected by immunofluorescence assay.Results(1)At each time point,the mNSS and the volume of cerebral infarction of the model group were significantly higher than those of the sham operation group (P<0.05),while the mNSS and the volume of cerebral infarction of the BMMNCs group were lower than those of the model group,higher than those of the sham operation group,and it was gradually decreased with the treatment time extension (P<0.05).There was no difference in comparison between the ERK1/2 inhibitor group and the model group (P>0.05).(2)At each time point,the pERK1/2,Bcl-2,Bax and caspase-3 protein levels of the model group were significantly higher than those of the sham operation group (P<0.05).The pERK1/2 and Bcl-2 protein levels of the BMMNCs group(pERK1/2:(0.38±0.16),(0.39±0.15),(0.40±0.20),Bcl-2:(0.38±0.14),(0.39±0.15),(0.37±0.13)) were higher than those of the model group(pERK1/2:(0.17±0.05),(0.14±0.04),(0.13±0.03),Bcl-2:(0.23±0.11),(0.24±0.12),(0.27±0.14),Bax:(0.39±0.13),(0.40±0.14),(0.45±0.23),caspase-3:(0.52±0.26),(0.56±0.27),(0.58±0.28)),while Bax and caspase-3 protein levels(Bax:(0.25±0.13),(0.19±0.06),(0.21±0.08),caspase-3:(0.35±0.13),(0.34±0.16),(0.29±0.09)) were decreased (P<0.05).The pERK1/2 protein level of ERK1/2 inhibitor group was lower than other groups,There was no difference in the level of Bcl-2,Bax and caspase-3 between the ERK1/2 group and the model group.(P>0.05).(3) At each time point,microglia (Iba1 positive) in ischemic penumbra of the BMMNCs group was significantly more than those of the model group,and it was increased with the time extension (P<0.05).There was no difference in comparison between the ERK1/2 inhibitor group and the model group (P>0.05).ConclusionBMMNCs can reduce the apoptosis through ERK1/2 signaling pathway,thus improving the neurological function and reducing the infarct scope.
