HIF-1α、ROCK-2、FoxM1在醋酸铅诱导PC12细胞损伤中的表达变化

发布时间：2018-03-31 16:11

本文选题：醋酸铅　切入点：PC细胞　出处：《中国药理学通报》2015年11期

【摘要】：目的探讨低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、Rho关联卷曲螺旋蛋白激酶-2(Rho associated coiled coil forming protein kinase-2,ROCK-2)、叉头蛋白M1(forkhead box protein M1,Fox M1)在醋酸铅[Pb(Ac)_2]诱导大鼠肾上腺嗜铬细胞瘤PC12细胞损伤中的表达和意义。方法将PC12细胞暴露于不同浓度的Pb(Ac)_2(100、200、400μmol·L~(-1))24 h以诱导细胞发生损伤。采用噻唑蓝比色法检测细胞的存活率,倒置显微镜观察细胞形态的变化,乳酸脱氢酶漏出率检测法测定细胞损伤程度,采用试剂盒检测丙二醛(malondialdehvde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)水平,Hoechst 33342单荧光染色法观察细胞凋亡,免疫印迹法检测细胞HIF-1α、ROCK-2、Fox M1、淋巴瘤/白血病-2(B cell lymphoma/leukemia,Bcl-2)和Bcl-2相关蛋白(Bcl-2 associated X protein,Bax)的表达。结果 MTT实验显示Pb(Ac)_2对PC12细胞具有明显抑制作用并呈剂量依赖性,与对照组相比,Pb(Ac)_2可增加细胞内LDH漏出率,升高MDA含量,降低SOD含量,诱导细胞发生凋亡。此外,Pb(Ac)_2上调细胞HIF-1α、ROCK-2的表达,下调Fox M1的表达,提高Bax/Bcl-2的表达比例。结论 Pb(Ac)_2诱导PC12细胞发生凋亡可能与HIF-1α、ROCK-2、FoxM 1的表达以及自由基损伤有关。
[Abstract]:Methods PC12 cells were exposed to different concentrations of Pb(Ac)_2(100200400 渭 mol L ~ (-1) for 24 h to induce cell damage.The survival rate of cells was measured by thiazolyl blue colorimetry, the morphological changes of cells were observed by inverted microscope, and the damage degree of cells was measured by lactate dehydrogenase leakage rate assay.In addition, PbAK can up-regulate the expression of HIF-1 伪 -roCK-2, down-regulate the expression of Fox M1, and increase the expression of Bax/Bcl-2.Conclusion the apoptosis of PC12 cells induced by Pb(Ac)_2 may be related to the expression of HIF-1 伪 -ROCK-2 and the damage of free radical.
【作者单位】：江苏大学医学院药理学教研室;
【基金】：国家自然科学基金资助项目(No 81300059) 江苏大学高级人才基金项目(No 08JDG005,11JDG092)
【分类号】：R96

【参考文献】