氯化镧对大鼠海马线粒体和死亡受体凋亡途径的影响  

Effects of lanthanum chloride on the mitochondrial and death receptor apoptotic pathways in the hippocampus of rats

作　　者：杨敬华[1] 刘秋芳[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教研室,辽宁沈阳110001

出　　处：《毒理学杂志》2014年第2期108-112,共5页Journal of Toxicology

基　　金：国家自然科学基金(81072316;81273117和81373024);辽宁省教育厅基金(L2010702和L2012290)

摘　　要：目的研究氯化镧(lanthanum chloride,LaCl3)对大鼠海马细胞凋亡和线粒体依赖的caspase-9、死亡受体依赖的caspase-8凋亡途径的影响,探讨LaCl3对海马产生毒性作用的机制。方法 40只Wistar雌性成年大鼠随机分成对照和低、中、高剂量LaCl3染毒组。对照孕鼠产仔后饮用蒸馏水,低、中、高剂量LaCl3染毒组孕鼠产仔后分别饮用0.25%、0.50%和1.00%LaCl3溶液。LaCl3染毒组子代大鼠断乳前吸吮母乳染镧,断乳后则通过自行饮用0.25%、0.50%和1.00%LaCl3蒸馏水溶液染镧,至断乳后1个月结束。取子代大鼠海马,采用流式细胞仪测定细胞凋亡率,采用比色法测定线粒体和胞浆内Cyt c含量,采用Western blot法检测Fas、FasL、caspase-3、caspase-8、caspase-9蛋白表达水平。结果 LaCl3染毒组子代大鼠海马细胞凋亡率显著高于对照组,且随染毒剂量增加而升高。低剂量LaCl3染毒组子代大鼠海马细胞线粒体内Cyt c含量显著低于对照组,而胞浆中Cyt c含量和caspase-3、caspase-9蛋白表达水平显著高于对照组;中剂量LaCl3染毒组子代大鼠海马细胞线粒体内Cyt c含量显著低于对照组和低剂量LaCl3染毒组,而胞浆中Cyt c含量和caspase-3、caspase-9蛋白表达水平显著高于对照组和低剂量LaCl3染毒组;高剂量LaCl3染毒组子代大鼠海马细胞线粒体内Cyt c含量显著低于对照组和低、中剂量LaCl3染毒组,而胞浆中Cyt c含量和caspase-3、caspase-9蛋白表达水平显著高于对照组和低、中剂量LaCl3染毒组。各LaCl3染毒组子代大鼠海马Fas、FasL和caspase-8蛋白表达水平均与对照组无显著性差异。结论 LaCl3染毒造成大鼠海马细胞凋亡过度的机制可能涉及线粒体caspase-9凋亡途径表达增强,而与死亡受体Fas依赖的caspase-8凋亡途径无关。Objective To study the effects of lanthanum chloride （ LaCl3 ） on apoptosis, mitochondrial caspase-9 and death receptor caspase-8 apoptotic pathway in the hippocampus of rats, and discuss the mechanism underlying the LaCl3-induced impairment in the hippocampus. Methods 40 Wistar female adult rats were divided randomly into four groups： control, low-, middle-, and high-dose LaCl3 groups. The control lactational rats were given with distilled water, and lactational rats in the low-, middle-, and high-dose LaCl3 groups were administrated with 0. 25% , 0. 5% and 1.0% LaCl3 in drinking water. Pups of LaCl3groups were administrated with LaCl3 by parental lactation and then were administrated with 0. 25% ,0. 5% and 1.0% LaCl3 in drinking water for one month after weaning. The hippocampi of pups were used for all determinations. Cellular apoptotic rate was determined by flow cytometry. Cyt c levels in the mitochondria and cytoplasm were measured by chromatometry, and Fas, FasL, caspase-3, caspase-8 and caspase-9 expression levels were analyzed by Westernblotting. Results Cellular apoptotic rates in the hippoeampus of LaCl3 groups were significantly higher than that of control group, and increased with LaCl3-dose increasing. Mitochondrial Cyt c levels in the hippocampus of low-dose LaCl3 group were significantly lower than that of control group, however cytoplasmic Cyt e levels, caspase-3 and easpase-9 expression levels in the hippoeampus of low-dose LaCl3 group were significantly higher than those of control group. Mitochondrial Cyt c levels in the hippocampus of middle-dose LaCl3 group were significantly lower than that of control and low-dose LaCl3 groups, however cytoplasmic Cyt c levels, caspase-3 and caspase-9 expression levels in the hippocampus of middle-dose LaCl3 group were significantly higher than those of control and low-dose LaCl3 groups. Mitochondrial Cyt c levels in the hippocampus of high-dose LaCl3 group were significantly lower than that of control, low-and middle-dose LaCl3 groups, however cytopl

关 键 词：氯化镧 大鼠 海马 凋亡 CASPASE 

分 类 号：R994.6[医药卫生—毒理学]