CAJ | 학술논문

目的:观察不同浓度拉莫三嗪(Lamotrigine,LTG)对体外培养海马神经细胞存活影响及脑源性神经生长因子(Brain derived neurotrophic factor,BDNF)和磷酸化cAMP反应元件结合(Phosphorylated cAMP response element binding protein,p-CREB)的表达变化.从细胞水平角度探索拉莫三嗪对认知功能的可能影响.方法:取培养8 d的成熟海马神经细胞,随机分为拉莫三嗪低剂量组(4mg/L)、拉莫三嗪中剂量组(8mg/L)、拉莫三嗪高剂量处理组(12mg/L)和空白对照组(0.1%DMSO).维持浓度培养4 d后,MTT法检测细胞存活数量,免疫组化检测神经细胞BDNF和p-CREB.结果:(1)不同浓度拉莫三嗪处理组与空白对照组之间比较,细胞存活率有明显差异(P<0.05).而3个不同剂量拉莫三嗪组之间的细胞存活率没有显著差异(P>0.05).(2)与正常对照组比12 mg/L拉莫三嗪培养神经细胞,p-CREB和BDNF的表达显著降低(P<0.05),而4、8 mg/L拉莫三嗪剂量组无差异(P>0.05).(3)加入拉莫三嗪12 mg/L培养神经细胞BDNF和p-CREB的表达明显低于4、8 mg/L拉莫三嗪剂量组(P<0.05).结论:在4～12 mg/L的剂量范围内,拉莫三嗪均可造成体外培养神经细胞死亡,高浓度拉莫三嗪可通过神经细胞内BDNF和p-CREB的表达变化,影响神经细胞存活.
목적:관찰불동농도랍막삼진(Lamotrigine,LTG)대체외배양해마신경세포존활영향급뇌원성신경생장인자(Brain derived neurotrophic factor,BDNF)화린산화cAMP반응원건결합(Phosphorylated cAMP response element binding protein,p-CREB)적표체변화.종세포수평각도탐색랍막삼진대인지공능적가능영향.방법:취배양8 d적성숙해마신경세포,수궤분위랍막삼진저제량조(4mg/L)、랍막삼진중제량조(8mg/L)、랍막삼진고제량처리조(12mg/L)화공백대조조(0.1%DMSO).유지농도배양4 d후,MTT법검측세포존활수량,면역조화검측신경세포BDNF화p-CREB.결과:(1)불동농도랍막삼진처리조여공백대조조지간비교,세포존활솔유명현차이(P<0.05).이3개불동제량랍막삼진조지간적세포존활솔몰유현저차이(P>0.05).(2)여정상대조조비12 mg/L랍막삼진배양신경세포,p-CREB화BDNF적표체현저강저(P<0.05),이4、8 mg/L랍막삼진제량조무차이(P>0.05).(3)가입랍막삼진12 mg/L배양신경세포BDNF화p-CREB적표체명현저우4、8 mg/L랍막삼진제량조(P<0.05).결론:재4～12 mg/L적제량범위내,랍막삼진균가조성체외배양신경세포사망,고농도랍막삼진가통과신경세포내BDNF화p-CREB적표체변화,영향신경세포존활.
Objective:To explore the possible effections on neuron survival rate and the change of BDNF and p-CREB induced by different concentrations of lamotrigine. Methods: The hippocampus was harvested from newborn Sprague - Dawley rats. Primary hippocampal neuron cultured for 8 days in vitro were used and divided randomly into four groups: low concentration (4 mg/L) group, middle concentration (12 mg/L) group, high concentration (12 mg/L) group and 0.1%DMSO as control. The BDNF and p-CREB levels were determined by immunohistochemistry and the cell survival rate was tested by MTT. Results: (1)compared with that in the control group, the survival of the neuron cell in all the lamotrigine groups decreased significantly (P<0.05),but the differences of survival rate was not great among the three lamotrigine groups. (2) Compared with the control group, expression of BDNF and p-CREB on the cell in the high concentration group were significantly different from those in the control group (P<0.05). (3) BDNF and p-CREB expressing on the cell in the 12 mg/L lamolrigine concentration group were significantly different from those in the 4 mg/L and 8 mg/L lamotrigine concentration group (P<0.05). Conclusion: In the leveT of 4-12 mg/L, lamtrigine can cause the neural cell death in vitro and the high concentration of lamotrigine (12 mg/L) causes the cell death by changing the expression of BDNF and p-CREB