第10号染色体同源丢失性磷酸酶张力蛋白基因在镉对小鼠神经功能影响中的作用

Effect of phosphatase and tensin homolog deleted on chromosome ten on the neurological function induced by cadmium of mice

目的探讨镉对小鼠神经功能的影响以及第10号染色体同源丢失性磷酸酶张力蛋白基因(phosphatase and tensin homolog deleted on chromosome ten,PTEN)是否参与其毒性作用。方法健康成年ICR小鼠24只,按体重随机分为4组,以0、0.5、1.0和2.0 mg/kg CdCl_2腹腔注射染毒14天,每天一次。末次染毒后Weaver's15分法进行神经功能评分,评分后,取脑组织,测定大脑丙二醛(MDA)、谷胱甘肽(GSH)含量以及过氧化氢酶(CAT)、总超氧化歧化酶(T-SOD)活性,实时荧光定量PCR和Western blotting检测PTEN表达。结果CdCl_22.0 mg/kg剂量组体重增长水平[(-0.6±0.9)g]显著下降,低于其他各组(F=9.211,P<0.05);与对照组相比,2.0 mg/kg CdCl_2组MDA水平[(19.3±3.7)nmol/mg pro]显著增加(F=4.123,P<0.05),GSH水平下降[(81.1±8.2)mg/g pro](F=7.644,P<0.05);1.0 mg/kg CdCl_2组CAT水平[(56.0±8.5)U/mg pro]低于对照组和0.5 mg/kg组(F=3.542,P<0.05);Western blotting显示2.0 mg/kg CdCl_2组磷酸化PTEN(p-PTEN(Ser380))表达水平提高(F=389.2,P<0.05)。结论镉至少部分通过激活PTEN脂质磷酸酶活性对神经系统产生损伤。

Objective To explore the effect of cadmium on nerve function and whether the phosphatase and tensin homolog deleted on chromosome ten (PTEN)was involved in its toxicity.Methods The healthy adult ICR mice were randomly divided into 4groups which included CdCl2 0,0.5,1.0 and 2.0mg/kg,all the mice were intraperitoneally injected administration every day for 14 days.15-point disease score scale were used to assess neurological function,after the elevation,all the brain were removed and harvested,the level of MDA,CAT,GSH and T-SOD were elevated,qRT-PCR and western blotting were used to detected the expression of PTEN.SPSS 20.0 was used to analyze the data.Results The body weight in CDCl 22.0mg/kg group was (-0.6±0.9)g,was significant lower than the others(F =9.211,P <0.05);the level of MDA in 2.0mg/kg was increased[(19.3±3.7)nmol/mg pro ](F =4.123,P <0.05)and GSH [(81.1±8.2)mg/g pro]decreased compared with the blank(F =7.644,P <0.05); the level of CAT in 1.0mg/kg[(56.0±8.5)U/rag pro]was decreased compared with the blank and 0.5mg/kg (F =3.542,P <0.05);the level of p-PTEN (Ser380)was significantly improved in western blotting(F =389.2,P <0.05).Conclusion Cadmium cause the damage to the nervous system at least partially by activating the lipid phosphatase activity of PTEN.