Neuroprotectin D1对异丙酚诱导海马神经元细胞保护作用机制研究  

Protective effects and mechanisms of Neuroprotectin D1 on hippocampal neurons induced by propofol

作　　者：张国梁 谢金兰 ZHANG Guo-liang;XIE Jin-lan(Department of Anesthesiology,Jinan People's Hospital,Jinan 271100,Shandong Province,China)

机构地区：[1]济南市人民医院麻醉科,山东济南271100

出　　处：《中国临床药理学杂志》2020年第13期1857-1860,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的分析不同浓度Neuroprotectin D1(NPD1)通过磷脂酰肌醇-3激酶/糖原合成激酶-3β(PI3K/GSK3β)信号通路对异丙酚诱导海马神经元细胞保护作用及其机制。方法按照随机数表法将体外原代培养大鼠海马神经元细胞分成6组:空白组、异丙酚组和第1实验组至第4实验组。空白组不做任何处理,异丙酚组加入异丙酚100μmol·L^-1孵育3 h,第1实验组至第4实验组分别加入4个不同浓度(25,50,75和100 nmol·L^-1)NPD1,再加入异丙酚100μmol·L^-1后孵育3 h。用流式细胞仪检测细胞凋亡率,以蛋白质印迹法检测细胞中GSK3β、PI3K蛋白表达水平(灰度值)。结果空白组、异丙酚组和第1实验组至第4实验组的细胞凋亡率分别为(12.03±3.10)%,(32.19±3.28)%,(21.43±3.09)%,(18.70±3.36)%,(17.90±3.14)%和(16.55±3.05)%;这6组的GSK-3β蛋白表达量分别为1.85±0.10,1.51±0.09,1.76±0.09,1.83±0.10,1.92±0.08和1.98±0.11;这6组的PI3K蛋白表达量分别为0.96±0.08,0.31±0.09,0.58±0.07,0.63±0.09,0.70±0.06和0.74±0.08。上述指标:异丙酚组与空白组比较,或第1实验组至第4实验组与异丙酚组比较,差异均有统计学意义(均P<0.05)。基因结果的趋势与蛋白一致。结论NPD1可降低异丙酚诱导海马神经元细胞细胞凋亡率,改善神经元受损程度,其作用机制可能与激活PI3K/GSK3β信号通路有关。Objective To detect the protective effect and mechanism of Neuroprotectin D1(NPD1)on propofol-induced hippocampal neurons through the phosphatidylinositol-3 kinase/glycogen synthase-3β(PI3 K/GSK3β)signaling.Methods The hippocampal neurons were divide to six groups according to random number table:blank group,propofol group(100μmol·L^-1 of propofol),and experimental-1,-2,-3,-4 groups(25,50,75,100 nmol·L^-1 of NPD1+100μmol·L^-1 of propofol),for incubation of 3 h.The apoptosis rate was tested by flow cytometry.The expression(gray value)of GSK3βand PI3 K proteins were observed by Western blot.Results The apoptotic rates in blank group,propofol group,and experimental-1,-2,-3,-4 groups were(12.03±3.10)%,(32.19±3.28)%,(21.43±3.09)%,(18.70±3.36)%,(17.90±3.14)%and(16.55±3.05)%;the expression levels of GSK-3βprotein in the six groups were 1.85±0.10,1.51±0.09,1.76±0.09,1.83±0.10,1.92±0.08 and 1.98±0.11;the expression levels of PI3 K protein in six groups were 0.96±0.08,0.31±0.09,0.58±0.07,0.63±0.09,0.70±0.06 and 0.74±0.08.Comparison between propofol group and blank group,or between experimental-1,-2,-3,-4 groups and propofol group,the difference of the factors were significant(all P<0.05).The trend of genetic results is consistent with that of proteins.Conclusion NPD1 can reduce the apoptosis rate of hippocampal neurons induced by propofol and improve the degree of neuronal damage.The mechanism may be related to the activation of PI3 K/GSK3βsignaling pathway.

关 键 词：异丙酚 海马神经元细胞 Neuroprotectin D1 神经毒性 磷脂酰肌醇-3激酶/糖原合成激酶-3β信号通路 

分 类 号：R97[医药卫生—药品]