不同浓度二甲双胍对丙泊酚所致斑马鱼神经毒性的改善作用

Effect of metformin at different concentrations on propofol-induced neurotoxicity in zebrafish

目的探讨不同浓度二甲双胍对丙泊酚所致斑马鱼神经毒性的改善作用。方法将150个受精后6 h(6 hpf)野生型AB品系斑马鱼胚胎按随机抽样法分别置于6孔板中,每孔30个,每组一孔,共5组。将5组分为二甲双胍500μg/ml(M1组)、1000μg/ml(M2组)、2000μg/ml(M3组)、丙泊酚对照组(P组)和正常对照组(C组),其中P组、M1组、M2组及M3组均加入丙泊酚5μg/ml,C组不作任何处理。培养1 d后记录斑马鱼胚胎中枢神经细胞凋亡数目。另将150个斑马鱼胚胎分组及处理同上,培养5 d后记录斑马鱼20 min内2个明暗周期(即黑暗5 min、光照5 min交替2个周期)每分钟平均运动速度,评估反应能力。结果与C组比较,P组中枢神经细胞凋亡增多(P<0.01);与P组比较,M3组中枢神经细胞凋亡数目明显减少(P<0.01)。与C组比较,P组每分钟平均运动速度明显减慢(P<0.01);与P组比较,M2组及M3组每分钟平均运动速度增快(均P<0.05)。结论2000μg/ml二甲双胍可以同时改善丙泊酚所致斑马鱼中枢神经细胞凋亡及反应能力降低。

Objective To evaluate the effect of metformin at different concentrations on propofol-induced neurotoxicity in zebrafish.Methods Wild type AB strain zebrafish embryos(6 h after fertilization)were randomly divided into 5 groups:group C,group P,group M1,group M2 and group M3 with 30 embryos in each.All groups except C,were treated with 5μg/ml of propofol,then groups M1,M2 and M3 were given metformin 500μg/ml,1000μg/ml or 2000μg/ml,respectively.The number of apoptotic central nerve cells was observed after 1 day.After 5 days,the average movement speed of zebrafish in 2 light and dark cycles(5 min in dark and 5min in light alternatively)was calculated.Results Compared with group C,the number of apoptotic cells in central nervous system of group P was increased(P<0.01).Compared with group P,the number of apoptotic cells in central nervous system of group M3 was significantly decreased(P<0.01).The average speed of movement in group P was significantly slower than that in group C(P<0.01).The average movement speed in group M2 and group M3 was increased compared with group P(P<0.05).Conclusion Metformin 2000μg/ml can alleviate the neurotoxicity induced by propofol in zebrafish.