喹硫平对脂多糖损伤后海马神经干细胞的保护作用

目的：探讨喹硫平（QUE）对脂多糖（LPS）损伤后海马神经干细胞（NSCs）活性的作用及增殖情况的影响，并初步研究胞外信号调节激酶（ERK ）信号通路在其中的作用。方法建立体外大鼠海马NSCs的LPS损伤细胞模型，分为对照组（Sham组）、LPS组、LPS＋ QUE组（包括0．5μmol／L、1μmol／L和2μmol／L三个不同剂量组），作用48 h后，采用WST －8试剂检测细胞活性，蛋白质印迹（Western Blot）法检测磷酸化胞外信号调节激酶1／2（pERK1／2）的表达水平，5－溴脱氧尿嘧啶核苷（BrdU ）检测细胞增殖情况。并在培养基中添加ERK磷酸化抑制剂U0126，以进一步明确ERK信号通路在其中的作用。结果（1）细胞活力：与Sham组[吸光度值（0．371±0．027）]相比，LPS组（0．251±0．034）细胞活力显著下降（P ＜0．01），而 LPS＋ QUE 1μmol／L 组（0．311±0．018）和 LPS＋ QUE 2μmol／L组（0．343±0．021）均显著抑制了LPS对其活力的影响（与LPS组相比，P＜0．05）。（2）West‐ern Blot结果显示，LPS组的pERK1／2表达水平（0．313±0．124）明显低于Sham组（1．417±0．141）及LPS＋QUE 1μmol／L组（0．681±0．098）组和LPS＋QUE 2μmol／L组（0．954±0．119）（P＜0．05），而LPS组与LPS＋QUE 0．5μmol／L组（0．368±0．123）的pERK1／2表达水平接近。（3）BrdU 染色结果显示，LPS组的BrdU阳性细胞数百分比（23．098±2．153）％明显低于Sham组（40．388±2．910）％， LPS＋QUE 1μmol／L 组（28．742±1．536）％和 LPS＋ QUE 2μmol／L 组（31．369±2．313）％（P ＜0.05）。（4）U0126可抑制QUE（1μmol／L和2μmol／L）的上述作用。结论 QUE能抑制LPS导致的NSCs损伤，这种作用与调节ERK1／2的磷酸化有关。

Protective effects of quetiapine on the lipopolysaccharide injured hippocampal -derived neural stem cell

Objective To explore the effects of quetiapine(QUE) on viability and proliferation in LPS injured hippocampal -derived neural stem cells (NSCs) and investigate the role of ERK signal path‐way .Methods The NSCs were derived from hippocampus of fetal rats ,and divided into Sham group , LPS group and LPS+QUE group (including 0 .5 ,1 and 2μmol/L) .Then the cell viability ,the expres‐sion of pERK1/2 and BrdU labeling and detection were measured by the kit of WST -8 ,Western Blot and immunocytochemical method after 48 h ,respectively .Furthermore ,the cell viability and BrdU labe‐ling and detection were also detected after U 0126 treatment to clear the role of ERK signal pathway .Re‐sults (1)Cell viability test showed that the viability of LPS group [A= (0 .251 ± 0 .034) ] was signifi‐cantly lower than that of Sham group [A= (0 .371 ± 0 .027)] ,LPS+ QUE 1μmol/L group [A= (0 .311 ± 0.018)] and LPS+QUE 2 μmol/L group [A= (0 .343 ± 0 .021)] (P < 0 .05) .(2)The expression of pERK1/2 in LPS group (0 .313 ± 0 .124) was significantly lower than that of Sham group (1 .417 ± 0.141) ,LPS+QUE 1μmol/L group (0 .681 ± 0 .098) and LPS+QUE 2μmol/L group (0 .954 ± 0 .119) as detected by Western Blot .(3)The percentage of BrdU+ cells in LPS group (23 .098 ± 2 .153)% was significantly lower than that of Sham group (40 .388 ± 2 .910)% ,LPS+ QUE 1 μmol/L group (28 .742 ± 1 .536)% and LPS+QUE 2μmol/L group (31 .369 ± 2 .313)% .(4)The effects of QUE (1μmol/L and 2μmol/L) were inhibited by U0126 .Conclusions The damage of cell viability and proliferation of NSCs induced by LPS can be restrained by QUE ,and this effect might be related to the activation of ERK sig‐naling pathw ay .