目的:研究氟化钠对Wistar大鼠心肌细胞凋亡的影响,并初步探讨其机制。方法:40只34周龄健康雄性Wistar大鼠,随机分为氟化钠25、50、100、150mg·L-14个实验组和一个对照组,实验组每日饮用含不同氟化钠浓度的蒸馏水,对照组饮用正常蒸馏水,复制慢性氟中毒大鼠动物模型。实验开始和6个月时各描记心电图一次,实验期结束后处死各组大鼠切取心肌组织;采用脱氧核糖核苷酸末端转移酶介导dUTP的缺口末端标记法(TdT-mediated dUTP nick end labeling,TUNEL)测定心肌细胞凋亡情况。运用流式细胞术(Flow cytometry,FCM)定量检测p53蛋白表达。结果:(1)心电图显示:氟化钠100 mg·L-1和150mg·L-1组氟中毒大鼠Q-T间期与对照组相比明显缩短(P〈0.05)。(2)氟化钠100mg·L-1组和150mg·L-1组心肌细胞凋亡指数明显高于对照组(P〈0.01),且相关基因p53的表达也明显高于对照组(P〈0.01)。结论:氟可导致心肌细胞凋亡,p53参与并介导细胞凋亡。
Objective:To study the effects of exposure of rats to fluoride on myocardial apoptosis and its mechanism.Methods:Forty 3~4-week-old male Wistar rats were randomly divided into 4experimental groups:25,50,100,150mg·L-1sodium fluoride(NaF)group and control group.All the experimental groups were fed with distilled water containing different concentrations of NaF respectively,and the control group with normal distilled water in order to duplicate the animal model of drinking water type fluorosis.Electrocardiogram(ECG)was taken before and after experiment for 6months to observe ECG of the rats with fluorosis.Apoptotic cardiomyocytes were detected with TUNEL and the protein expression of p53 in cardiomyocytes was determined by the techniques of flow cytometry.Results:(1)As compared with control group,the Q-T interval in 100mg·L-1group and 150mg·L-1group were markedly shorter(P〈0.05).(2)As compared with control group,the apoptosis rate of cardiomyocytes in 100mg·L-1group and150mg·L-1group were significantly increased(P〈0.01),accompanied with an increased expression of p53(P〈0.01).Conclusion:Fluorosis can induce myocardial apoptosis,p53 may be involved in the regulation of the apoptotic process.