Effects of monocarboxylate transporter 1 on the proliferation,migration and differentiation of astrocytes after spinal cord injury in rats
Objective To investigate the effect and mechanism ot regulation of lactate transport by monocarboxylate transporter 1(MCT1)on the differentiation of astrocytes(AS)after spinal cord injury(SCI)in rats.Methods Adult female Sprague-Dawley(SD)rats were purchased from the Laboratory An-imal Center of Shanxi Medical University.SCI model was established by modified Allen's method and di-vided into sham operation group,SCI(12 h)group,SCI+LA group and SCI+AZD group with 5 rats in each group.The effects of intraperitoneal injection of exogenous sodium lactate or MCT1 inhibitor on the differentiation of spinal cord AS in rats after SCI were observed.The spinal cord AS of SD rats were cul-tured and the oxygen glucose deprivation/reoxygenation(OGD/R)model was established.First,the lactate content and MCT1 expression of AS treated with OGD/R at different time points were observed.Secondly,the effect of adding exogenous sodium lactate or MCT1 inhibitor after OGD/R on AS differentiation was ob-served,and normal group,OGD/R(OGD4.5 h/R12 h)group,OGD/R+sodium lactate group,OGD/R+sodium lactate+AZD group were set up.Finally,the effects of Bay 11-7082(NF-κB inhibitor)or Stattic(STAT3 inhibitor)pathway proteins on AS differentiation were analyzed,and OGD/R+sodium lactate group,OGD/R+sodium lactate+BAY group,OGD/R+sodium lactate+STA group were set up.One-way analysis of variance was used for statistical analysis,and Tukey's test was used for pairwise com-parison.Results In SCI 12 h group,the expression of spinal cord MCT1 was higher than in sham group(2.776±0.353 vs.1.000,q=13.460,P＜0.01).In SCI+LA group,the expression of spinal cord MCT1(2.767±0.208 vs.1.900±0.100,q=10.840,P＜0.01)and S100A10 protein(1.933±0.153 vs.1.630±0.061,q=5.924,P＜0.05)were higher than in SCI group,and that of C3 was lower than in SCI group(1.603±0.035 vs.1.830±0.147,q=4.561,P＜0.05).In SCI+AZD group,the expres-sion of MCT1(1.233±0.153 vs.1.900±0.100,q=8.341,P＜0.05)and S100A10 protein(1.237±0.067 vs.1.630±0.061,q=7.681,P＜0.01)was lower than in SCI group,and that of C3 was higher than in SCI group(2.340±0.082 vs.1.830±0.147,q=10.260,P＜0.01).In the OGD4.5 h/R12 h group,the expression of MCT1 was higher than in normal group(1.760±0.053 vs.1.000,q=6.415,P＜0.01).In OGD/R+LA group,the intracellular lactate content of AS(0.028±0.001 vs.0.022±0.001,q=6.415,P＜0.01),the expression of MCT1(2.200±0.100 vs.1.633±0.058,q=13.870,P＜0.01)and p-STAT3 protein(3.400±0.173 vs.2.133±0.252,q=12.850,P＜0.01)were higher than in OGD/R group,the expression of nuclear NF-κB protein was lower than in OGD/R group(1.153±0.129 vs.1.933±0.153,q=12.100,P＜0.01),A1 differentiation was lower than in OGD/R group(1.133±0.058 vs.1.600±0.100,q=7.000,P＜0.01),and A2 differentiation was higher than in OGD/R group(2.300±0.173 vs.1.433±0.058,q=15.920,P＜0.01).In OGD/R+LA+AZD group,the intracellular lactate content of AS(0.014±0.002 vs.0.022±0.001,q=9.278,P＜0.01),the expression of MCT1(1.430±0.082 vs.1.633±0.058,q=4.976,P＜0.01)and p-STAT3 protein(1.533±0.153 vs.2.133±0.252,q=6.085,P＜0.05)were lower than in OGD/R group,nuclear NF-κB protein was higher than in OGD/R group(2.400±0.100 vs.1.933±0.153,q=7.239,P＜0.01),A1 differentiation was higher than in OGD/R group(2.200±0.200 vs.1.600±0.100,q=9.000,P＜0.01),A2 differentiation was lower than in OGD/R group(1.133±0.047 vs.1.433±0.058,q=5.510,P＜0.05).In OGD/R+LA+BAY group,A1 differentiation was lower than in OGD/R+LA group(0.846±0.050 vs.1.000,q=6.527,P＜0.01),and A2 differentiation was higher than in OGD/R+LA group(1.300±0.100 vs.1.000,q=7.491,P＜0.05).In OGD/R+LA+STA group,A1 differentiation was higher than in OGD/R+LA group(1.177±0.049 vs.1.000,q=7.520,P＜0.01),and A2 differentiation was lower than in OGD/R+LA group(0.813±0.066 vs.1.000,q=4.661,P＜0.01).Conclusion MCT1 regulates AS lactate transport after SCI,and increased intracellu-lar lactate content in AS can promote the differentiation to A2 of AS,which can be achieved by NF-κB/STAT3 signaling pathway.
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