硒对氟致大鼠肝脏损伤的保护作用

Protective Effect of Selenium on Liver Impairments Induced by Sodium Fluoride in Rats

目的探讨硒对氟致大鼠肝脏损伤的保护作用,探寻硒的最佳作用剂量及可能的作用靶点。方法将240只健康初断乳清洁级SD雄性大鼠随机分成8组,分别为溶剂对照(自来水,含氟量<0.2 mg/L,含硒量<1μg/L)组,氟(50 mg/L)单独染毒组,低(0.375 mg/L)、中(0.75 mg/L)、高(1.5 mg/L)浓度硒单独染毒组和低(0.375 mg/L)、中(0.75 mg/L)、高(1.5 mg/L)浓度硒+氟(50 mg/L)联合染毒组,每组30只。采用自由饮水方式进行染毒,连续染毒6个月。实验期间,大鼠进食标准饲料(氟含量<0.2 mg/kg,硒含量为0.1～0.2 mg/kg)。染毒结束后,测定肝脏中谷胱甘肽过氧化物酶(GSH-Px)、总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活力及丙二醛(MDA)含量及核转录因子κB(nuclear factor kappa B,NF-κB)表达水平。并观察氟中毒的一般症状和肝脏的病理学损伤。结果氟单独染毒组大鼠氟斑牙症状明显。与溶剂对照组相比,氟单独染毒组大鼠肝脏中GSH-Px、SOD活力降低,MDA含量升高,差异均有统计学意义(P<0.05);高浓度硒单独染毒组SOD活力降低,差异均有统计学意义(P<0.05)。与氟单独染毒组相比,高浓度硒+氟联合染毒组大鼠肝脏中GSH-Px活力上升,差异均有统计学意义(P<0.05);高浓度硒+氟联合染毒组MDA含量下降,差异均有统计学意义(P<0.05)。各染毒组大鼠肝脏中T-AOC活力间比较,差异无统计学意义。与溶剂对照组相比,氟单独染毒组和低浓度硒+氟联合染毒组大鼠肝组织中NF-κB表达水平升高,差异均有统计学意义(P<0.05)。与氟单独染毒组相比,中浓度硒+氟联合染毒组和高浓度硒+氟联合染毒组大鼠肝组织中NF-κB表达水平有所降低,但差异无统计学意义。病理学结果显示,氟+硒联合染毒组大鼠肝细胞变性坏死程度明显减轻,且肝细胞变性坏死程度随着硒染毒浓度的升高而呈下降趋势。结论 1.5 mg/L是在本实验条件下硒对氟致肝脏损伤的最佳保护作用剂量,NF-κB可能是硒拮抗氟中毒的药物靶点。

Objective To explore the protective effects of selenium,an antioxidant,on fluoride-induced liver injury in rats and find out the optimal level of selenium against fluoride toxicity and its possible valid molecular target.Methods Two hundred and forty healthy weaning clean SD rats were randomly divided into 8 groups,30 in each.The control group（tap water,fluoride content 0.2 mg/L,selenium content 1 μg/L）;fluoride（50 mg/L） single exposure group;the low（0.375 mg/L）,middle（0.75 mg/L）,high（1.5 mg/L） concentrations of selenium single exposure group and the low（0.375 mg/L）,middle（0.75 mg/L）,high（1.5 mg/L） selenium concentration combined with fluoride（50 mg/L） exposure group,and the treatments were conducted through drinking water for 6 months.During the experiment,rats were feed with the standard diet（fluoride content 0.2 mg/kg,selenium content of 0.1-0.2 mg/kg）.At the end of exposure,the levels of glutathione-peroxidase（GSH-Px）,total antioxidant capacity（T-AOC）,superoxide dismutase（SOD）,malondialdehyde（MDA）,and the nuclear transcription factor κB（NF-κB） expression in liver were determined.The general symptoms of fluorosis and the pathological liver injury were also observed.Results The group with fluoride single exposure showed obvious symptoms of dental fluorosis,and the activities of GSH-Px,SOD in rat liver decreased,the content of MDA increased（P0.05）;the activities of SOD in high dose group of single selenium reduced（P0.05）.Compared with single fluoride group,the activities of GSH-Px in rat livers groups with high concentration of combined selenium-fluoride exposure increased significantly（P0.05）;the contents of MDA in the moderate single selenium group and the group with high concentration of combined fluoride-selenium exposure were decreased（P0.05）.Compared with the control,the NF-κB expression in rat livers in single fluoride group and those with low selenium-fluoride exposure increased（P0.05）.Compared with fluoride single exposure group,the NF-κB expression in rat livers in single low selenium group decreased（P0.05）.Pathology results showed that the rats in groups of fluoride-selenium combined exposure significantly ameliorate the degeneration and necrosis of liver cells.Conclusion 1.5 mg/L Na2SeO3 is the optimal dose against fluorosis on liver injury under this experimental condition.NF-κB is likely to be a target molecule for selenium used as an antagonist to fluorosis.