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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 effect of selenium on liver injury induced by fluorine in rats and to explore the optimal dose of selenium and its possible target. Methods 240 male SD rats were randomly divided into 8 groups: solvent control group (tap water, fluoride content <0.2 mg / L, selenium <1 μg / L), fluoride group (50 mg / L, 0.375 mg / L, 0.75 mg / L and 1.5 mg / L selenium alone and 0.375 mg / L medium and 0.75 mg / L, 1.5 mg / L selenium + 50 mg / L, and 30 rats in each group. Using free drinking water for exposure, continuous exposure for 6 months. During the experiment, rats were fed standard diet (fluorine content <0.2 mg / kg, selenium content 0.1-0.2 mg / kg). After the exposure, the contents of glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) The expression of nuclear factor kappa B (NF-κB) And observed the general symptoms of fluorosis and liver pathological damage. Results Fluorosis in rats exposed to fluoride alone was obvious. Compared with the solvent control group, the activities of GSH-Px, SOD and MDA in the liver of the rats treated with fluoride alone were significantly lower than those of the control group (P <0.05) Reduce, the difference was statistically significant (P <0.05). Compared with the fluoride-alone group, the activities of GSH-Px in the liver of rats exposed to high concentrations of selenium + fluorine increased significantly (P <0.05) Content decreased, the difference was statistically significant (P <0.05). There was no significant difference in the T-AOC activity in the liver between the three exposure groups. Compared with the solvent control group, the expression of NF-κB in the liver of the rats treated with both fluoride-alone and low-concentration selenium + fluoride increased significantly (P <0.05). Compared with the fluoride-alone group, the expression of NF-κB in the hepatic tissue of the medium-concentration selenium + fluoride combined group and the high-concentration selenium + fluoride combined group were decreased, but the difference was not statistically significant. The results of pathology showed that the degree of hepatocyte degeneration and necrosis in the combination of fluoride and selenium was significantly reduced, and the degree of hepatocyte degeneration and necrosis decreased with the increase of selenium concentration. Conclusion 1.5 mg / L is the optimal protective dose of selenium against liver damage induced by fluoride under the experimental conditions. NF-κB may be the drug target of selenium antagonism against fluorosis.