氯化镧对大鼠星形胶质细胞内质网应激及凋亡的影响  

Effects of lanthanum chloride on endoplasmic reticulum stress and apoptosis in astrocytes of rats

作　　者：杨敬华[1] 果威旭 吕丹[1] 巫生文[1] 逯晓波[1] 靳翠红[1] 蔡原[1] 

机构地区：[1]中国医科大学公共卫生学院卫生毒理学教研室,辽宁沈阳110122

出　　处：《环境与健康杂志》2015年第8期659-662,共4页Journal of Environment and Health

基　　金：国家自然科学基金(81373024;81273117)

摘　　要：目的观察氯化镧(LaCl3)对大鼠大脑皮质星形胶质细胞(Ast)中葡糖调节蛋白-94(GRP-94)、蛋白激酶R样内质网激酶(PERK)、生长阻滞和DNA损伤诱导蛋白153(GADD153)、半胱天冬蛋白酶-12(caspase-12)表达的影响。方法分别用0、0.25、0.5、1.0 mmol/L LaCl3作用Ast细胞24 h,再以四甲基偶氮唑盐法检测Ast细胞活力,以流式细胞仪检测Ast细胞凋亡,以Western blotting法检测Ast细胞GRP-94、PERK、磷酸化PERK(pPERK)、GADD153和caspase-12的水平。结果 0.25、0.5、1.0 mmol/L LaCl3染毒后,Ast细胞活力降低,Ast细胞凋亡升高,均呈剂量-效应关系,差异均有统计学意义(P<0.05)。0.25、0.5、1.0 mmol/L LaCl3染毒组Ast细胞的GRP-94、pPERK、GADD153、caspase-12水平均高于对照组,其中1.0 mmol/L LaCl3染毒组上述指标分别为对照组的3.10、5.25、2.73、3.14倍,差异均有统计学意义(P<0.05)。结论 GRP-94、pPERK、GADD153和caspase-12表达上调使凋亡异常增多,其可能是LaCl3对Ast细胞产生毒作用的机制之一。Objective To survey the effects of lanthanum chloride（LaCl3） on glucose-regulated protein-94（GRP-94）, protein kinase R-like endoplasmic reticulum kinase（PERK）, growth arrest and DNA damage inducible protein 153（GADD153） and caspase-12 expression in astrocytes（Ast） of rats. Methods Ast cells were treated with LaCl3 at the doses of 0, 0.25, 0.5 and1.0 mmol/L respectively, for 24 h. The viability of Ast cell was detected with methyl thiazolyl tetrazolium assay and the apoptosis of Ast cell was detected with flow cytometry. Western blotting was used to detect GRP-94, PERK, phosphorylated PERK（pPERK）, GADD153 and caspase-12 in Ast cell. Results After LaCl3 exposure, the viability of Ast cells decreased（P〈0.05）, the apoptotic ratioes of Ast cells increased（P 〈0.05） significantly, with a dose dependent manner. GRP-94, pPERK,GADD153 and caspase-12 levels in 0.25, 0.5 and 1.0 mmol/L LaCl3-treated Ast cells were higher compared with control Ast cells（P〈0.05）. The GRP-94, pPERK, GADD153 and caspase-12 levels in 1.0 mmol/L LaCl3-treated Ast cells were 3.10 fold,5.25 fold, 2.73 fold and 3.14 fold of control values（P〈0.05）. Conclusion One possible mechanism is proposed that LaCl3 led to the enhanced apoptosis induced by up-regulation of GRP-94, pPERK, GADD153 and caspase-12 and then cause the toxic damage in the Ast cells.

关 键 词：氯化镧 GRP-94 PERK GADD153 

分 类 号：R994.6[医药卫生—毒理学]