镧对仔鼠皮质神经细胞BAX表达的影响
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摘要
通过对染镧仔鼠皮质组织BAX mRNA和BAX蛋白表达的检测,探讨镧暴露对仔鼠皮质神经细胞BAX表达的影响。取Wistar雌性大鼠32只,随机分成对照组及低、中、高剂量LaCl_3组,各LaCl_3组饮水中镧(用LaCl_3配制)浓度分别为0.25%、0.5%和1.0%,每组8只动物。实验动物以自由饮水的方式进行镧暴露。子代大鼠在断乳前经由母体血循环和吸吮母乳染镧,断乳后则通过自行饮水摄入。在整个实验过程中记录孕鼠及仔鼠体重,在仔鼠出生后49 d麻醉处死。取仔鼠皮质组织,应用实时定量PCR检测BAX mRNA、用Western-blot检测BAX蛋白表达水平变化。结果显示仔鼠皮质重量逐渐下降,高、中剂量LaCl_3组仔鼠皮质重量低于对照组,皮质系数逐渐增加,差异有统计学意义(P<0.05),这提示仔鼠脑发育已经受损。仔鼠皮质组织BAX mRNA和BAX蛋白表达在各剂量LaCl_3组之间出现差异,与对照组相比,高、中剂量LaCl_3组仔鼠皮质组织中BAX mRNA和BAX蛋白表达量明显增高,差异有统计学意义(P<0.05);且随着LaCl_3暴露剂量的增加,仔鼠皮质BAX mRNA和BAX蛋白表达水平逐渐上升,差异有统计学意义(P <0.05)。提示镧暴露导致的仔鼠大脑皮质发育损伤,可能与皮质BAX mRNA和BAX蛋白表达水平升高有关系。
To investigate the effect of lanthanum exposure on the expression of BAX,BAX mRNA and BAX protein in the cortical nerve cells of offspring rats were measured.Thirty-two Wistar female rats were randomly divided into control group and low,medium and high dose LaCl_3 groups.The concentration of lanthanum in water(prepared with LaCl_3) was 0.25%,0.5% and 1.0%,respectively.Experimental animals were exposed to lanthanum by free drinking water.The offspring rats were exposed to lanthanum with maternal blood circulation and sucking breast milk before weaning,and then ingested by self-drinking water after weaning.The weights of pregnant and pups were recorded throughout the experiment.The offspring were anesthetized on the 49th day after birth and their cortex tissue were taken.The expression of BAX mRNA was detected by real-time quantitative PCR and the expression of BAX protein was detected by Western-blot.The results showed that the cortical weight of the rats was gradually decreased.The cortical weights of the high and medium dose LaCl_3 group were lower than that of the control group,and the cortical coefficient was gradually increased,the difference was statistically significant(P<0.05),which indicated that the brain development of the offspring was impaired.The expression of BAX mRNA and BAX protein in the cortex of the rats were different among the groups.The expression of BAX mRNA and BAX protein in the cortical nerve cells of the high and medium dose LaCl_3 group were significantly increased when compared with the control group,the differences were statistically significant(P<0.05).With the increase of exposure dose,the expression levels of BAX mRNA and BAX protein in the cortex of the rats were gradually increased,and the differences were statistically significant(P<0.05).It is suggested that the developmental damage of the cerebral cortex in the offspring induced by lanthanum may be related to the increased expression of BAX mRNA and BAX protein in the cortex.
To investigate the effect of lanthanum exposure on the expression of BAX,BAX mRNA and BAX protein in the cortical nerve cells of offspring rats were measured.Thirty-two Wistar female rats were randomly divided into control group and low,medium and high dose LaCl_3 groups.The concentration of lanthanum in water(prepared with LaCl_3) was 0.25%,0.5% and 1.0%,respectively.Experimental animals were exposed to lanthanum by free drinking water.The offspring rats were exposed to lanthanum with maternal blood circulation and sucking breast milk before weaning,and then ingested by self-drinking water after weaning.The weights of pregnant and pups were recorded throughout the experiment.The offspring were anesthetized on the 49th day after birth and their cortex tissue were taken.The expression of BAX mRNA was detected by real-time quantitative PCR and the expression of BAX protein was detected by Western-blot.The results showed that the cortical weight of the rats was gradually decreased.The cortical weights of the high and medium dose LaCl_3 group were lower than that of the control group,and the cortical coefficient was gradually increased,the difference was statistically significant(P<0.05),which indicated that the brain development of the offspring was impaired.The expression of BAX mRNA and BAX protein in the cortex of the rats were different among the groups.The expression of BAX mRNA and BAX protein in the cortical nerve cells of the high and medium dose LaCl_3 group were significantly increased when compared with the control group,the differences were statistically significant(P<0.05).With the increase of exposure dose,the expression levels of BAX mRNA and BAX protein in the cortex of the rats were gradually increased,and the differences were statistically significant(P<0.05).It is suggested that the developmental damage of the cerebral cortex in the offspring induced by lanthanum may be related to the increased expression of BAX mRNA and BAX protein in the cortex.
引文
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[11]焦俊霞,高维娟.Bcl-2、Bax和Cyt-c在神经系统疾病中作用机制的研究进展[J].中国老年学杂志,2011,31(24):4982-4985.
[12]邵胜敏,王小同.Bcl-2基因家族在中枢神经系统中的作用[J].医学综述,2006(5):264-266.
[2]任丽宝,王小燕,解清.大鼠脑组织中轻稀土元素含量相关性研究[J].分析试验室,2007,26(7):108-111.
[3]杨敬华,吕丹,孙文昌,等.孕哺期及断乳后氯化镧暴露对大鼠大脑皮质神经细胞钙稳态及Bcl-2蛋白家族和caspase蛋白表达的影响[J].环境与健康杂志,2016,33(6):471-474.
[4]夏青,陈东,刘玉荣,等.混合“稀土”长乐对大鼠肝脏代谢的影响[J].毒理学杂志,2006,20(1):61-63.
[5]ZHENG L,YANG J,LIU Q,et al.Lanthanum chloride impairs spatial learning and memory,downregulates NF-κB signalling pathway in rats[J].Archives of Toxicology.2013,87(12):2105-2117.
[6]杨敬华,刘秋芳,巫生文,等.生长发育期氯化镧暴露对大鼠海马神经元和神经突触超微结构的影响[J].环境与健康杂志,2010,27(8):659-661.
[7]JIA D P,WANG S,ZHANG B C,et al.Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer’s disease[J].Exp Ther Med,2015,10:804-808.
[8]孔德亮,徐爱静,李娟,等.氟化钠通过调控Bcl-2和Bax基因的表达诱导大鼠肾脏细胞凋亡机制的研究[J].临床和实验医学杂志,2017,16(17):1676-1679.
[9]LIU L S,BAI X Q,GAO Y,et al.PCSK9 promotes oxLDL-induced PC12 cell apoptosis through the Bcl-2/Bax-Caspase 9/3 signaling pathway[J].Journal of Alzheimers Disease,2017,57(3):723.
[10]KHAZAEI S,RAMACHANDAN V,ABDUL H R,et al.Flower extract of Allium atroviolaceum triggered apoptosis,activated caspase-3 and down-regulated antiapoptotic Bcl-2 gene in HeLa cancer cell line[J].Biomedicine&Pharmacotherapy,2017,89:1216.
[11]焦俊霞,高维娟.Bcl-2、Bax和Cyt-c在神经系统疾病中作用机制的研究进展[J].中国老年学杂志,2011,31(24):4982-4985.
[12]邵胜敏,王小同.Bcl-2基因家族在中枢神经系统中的作用[J].医学综述,2006(5):264-266.