硒对镉诱导大鼠肝细胞端粒酶活力作用研究

Effects of selenium on telomerase activity induced by cadmium in rat hepatocytes

目的研究硒对镉诱导的大鼠肝细胞端粒酶活力、癌基因c-myc和p53表达的影响。方法 80只雄性SD大鼠随机分为16组,包括对照组,2.5、5.0和10.0μmol/kg亚硒酸钠组,5.0、10.0和20.0μmol/kg氯化镉组,9个硒镉联合作用组。氯化镉采用腹腔注射染毒、亚硒酸钠采用灌胃染毒。用端粒重复序列扩增法(TRAP)检测端粒酶活力,用逆转录聚合酶链反应法检测c-myc和p53表达。结果 3个镉单独作用组的大鼠肝细胞端粒酶活力、c-myc和p53表达较对照组明显增高,差异有统计学意义(P<0.05)。硒镉联合作用组中,当2.5和5.0μmol/kg亚硒酸钠分别与5.0、10.0和20.0μmol/kg氯化镉联合作用时,大鼠肝细胞端粒酶活力、c-myc和p53 mRNA水平较相应剂量的镉单独作用组下降;当10.0μmol/kg亚硒酸钠分别与5.0、10.0和20.0μmol/kg氯化镉联合作用时,大鼠肝细胞端粒酶活力、c-myc和p53 mRNA水平与相应剂量的镉单独作用组比较,差异无统计学意义(P>0.05)。结论相对较低剂量的硒对镉引起的大鼠肝细胞端粒酶活力增高具有抑制作用,其抑制作用可能是通过降低c-myc和p53表达。

Objective To study the effects of selenium on telomerase activity, expression of c-myc and p53 induced by cad- mium in rat hepatocytes. Methods 80 SPF free male SD rats were randomly divided into 16 groups, which included control group, 2. 5,5.0 and 10.0 μmol/kg Na2SeO3 groups, 5.0, 10.0 and 20.0 μmol/kg CdCI2 groups, and 9 joint action groups for selenium and cadmium. Cadmium was administrated intraperitoneally and selenium was given by gavage. Telomerase activity was measured by the telomeric repeat amplification protocol assay （TRAP）, and expression of c-myc and p53 were analysed by re- verse transcription-polymerase chain reaction. Results Compared with those of the control group, 5.0, 10. 0 and 20.0 μmol/ kg CdCl2 increased telomerase activities and induced over expressions of c-myc and p53 in rat hepatocytes significantly respective- ly （P 〈 0.05 ）. Compared with those of the corresponding cadmium treatment groups, 2. 5 and 5. 0 μmol/kg Na2SeO3 combined with 5. 0, 10. 0 and 20. 0 μmo//kg CdCl2 respectively, telomerase activities and the expressions of c-myc and p53 were de- creased. While 10. 0 μmol/kg Na2SeO3 combined with 5.0,10. 0 and 20. 0 μmol/kg CdC12 respectively, telomerase activities and the expressions of c-myc and p53 did not change significantly （ P 〉 0.05 ）. Conclusion Selenium at a relatively low dose may inhibit telomerase activity induced by cadmium in rat hepatocytes, and the inhibitive effects of selenium on cadmium may be mediated by decreasing the expressions of c-myc and p53.