CSF1通过CSF1R/PLCG2/ERK/Nrf2信号通路减少缺氧缺血性脑病大鼠神经元凋亡

目的:探讨集落刺激因子1(CSF1)通过CSF1受体(CSF1R)减轻缺氧缺血性脑病(HIE)大鼠神经元凋亡的下游信号通路.方法:采用原代大鼠皮质神经元建立氧糖剥夺(OGD)神经元损伤模型,重组人CSF1(rh-CSF1)干预该模型,通过CCK-8和MTT检测细胞活力,测定LDH漏出,Western blot检测CSF...

CSF1 attenuates neuronal apoptosis in hypoxic-ischemic encephalopathy through CSF1R/PLCG2/ERK/Nrf2 pathway

AIM:To explore the role of colony stimulating factor 1(CSF1)in reducing neuronal apoptosis after hypoxic-ischemic encephalopathy(HIE).METHODS:The primary rat cortical neurons were used to establish oxygen and glucose deprivation(OGD)-injured neuronal model. Recombinant human CSF1(rh-CSF1)was used to treat the cells. CCK-8,MTT and LDH leakage were used to determine the cell viability and apoptosis. Western blot was used to evaluate the protein levels of CSF1,CSF1 receptor(CSF1 R),phospholipase C gamma 2(PLCG2),extracellular signalregulated kinase 1/2(ERK1/2),nuclear factor E2-related factor 2(Nrf2),Bax,Bcl-2 and cleaved caspase-3. Rat HIE model was established,and Western blot was used to detect the expression of ERK1/2 and Nrf2 at 6 h,12 h,24 h,48 h,72 h and 7 d after modeling and the expression of ERK1/2,Nrf2,Bax,Bcl-2 and cleaved caspase-3 after treatment with rh-CSF1,BLZ945(CSF1 R blocker)and U73122(PLCG2 blocker).RESULTS:In vitrodata showed that compared with OGD group,rh-CSF1 significantly increased the cell viability and reduced LDH leakage(P<0. 05). Compared with OGD group,the protein levels of p-CSF1 R,p-PLCG2,p-ERK1/2,p-Nrf2 and Bcl-2/Bax were increased significantly,and cleaved caspase-3 was reduced(P<0. 05). Animal experiments showed that the levels of p-ERK1/2 and p-Nrf2 was increased after HIE,reached a peak at 24 h,and then gradually decreased. In addition,inhibition of CSF1 by CSF1 R blocker or PLCG2 blocker reduced the levels of p-ERK1/2,p-Nrf2 and Bcl-2/Bax in the brain tissue of HIE rats,but increased cleaved caspase-3 level(P<0. 05).CONCLUSION:rh-CSF1 reduces neuronal apoptosis via CSF1 R/PLCG2/ERK1/2/Nrf2 signaling pathway in HIE rats.