目的 研究氟化钠(NaF)中毒对大鼠肾脏细胞凋亡的影响,并从抗凋亡的角度探究其凋亡的机制.方法 48只体重80~100 g的雄性SD大鼠,随机分成四组:对照组、低氟组、中氟组、高氟组,每组12只,分别饮用浓度为0 mg/L、50 mg/L、100 mg/L、200 mg/L NaF的去离子水,连续染毒120 d.观察大鼠的一般状态,氟斑牙形成情况,测量体重变化及尿氟含量;制备肾脏细胞悬液,用流式细胞术检测肾脏细胞凋亡率;实时荧光定量RT-PCR和Western blot检测肾脏组织中Bcl-2和Bax基因的表达.结果 在氟化钠染毒的第60天和120天,髙氟组大鼠体重显著低于对照组(P<0.05);三个NaF处理组氟斑牙发生率、尿氟含量及肾脏细胞凋亡率均显著高于对照组(P<0.05);随着氟化钠浓度的升高,Bcl-2 mRNA和蛋白的表达呈现上调趋势,而Bax mRNA和蛋白的表达则呈下调趋势,并且差异具有显著性(P<0.05).结论 氟化钠可通过抑制Bcl-2和促进Bax的表达诱导肾脏细胞凋亡,并且随着氟化钠浓度的升高,凋亡率逐渐升高.%Objective To study the effect of NaF poisoning on renal cell apoptosis in rats, and the mechanism of apoptosis was investigated from the point of view of anti apoptosis.Methods 48 male SD rats weighing between 80~100 g, the rats were randomly divided into 4 groups: control group, low fluoride group, medium fluoride group and high fluoride group, 12 rats in each group, and deionized water of 0 mg/L, 50 mg/L, 100 mg/L and 200 mg/L NaF respectively, continuous exposure to 120 d.The general state of the rats was observed, the formation of dental fluorosis, weight change and urine fluoride content were measured;preparation of renal cell suspension, the apoptosis rate of renal cells was measured by flow cytometry.Real time fluorescence quantitative RT-PCR and Western blot were used to detect the expression of Bcl-2 and Bax genes in renal tissues.Results 60 d and 120 d in NaF exposure, the weight of high fluoride group rats were significantly lower than the control group (P<0.05).The dental fluorosis incidence, the fluoride content in the urine and renal cell apoptosis rate of the three NaF treatment group were significantly higher than control group (P<0.05).With the increase of sodium fluoride concentration, the expression of Bcl-2 mRNA and protein showed an upward trend, the expression of Bax mRNA and protein showed a downward trend, and the difference was significant (P<0.05).Conclusion NaF can induce apoptosis of renal cells by inhibiting Bcl-2 and promoting the expression of Bax, and with the increase of sodium fluoride concentration, the apoptosis rate increased gradually.
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