摘要
目的研究饮水氟染毒对大鼠肝、肾细胞周期阻滞的时间-效应和剂量-效应。方法将60只健康SPF级雄性SD大鼠随机分为4组,分别为对照(蒸馏水)组和低(10 mg/L)、中(50 mg/L)、高浓度(100 mg/L)氟化钠染毒组,每组15只。采用自由饮水方式进行染毒,连续染毒120 d。采用流式细胞术检测肝、肾细胞周期分布,并计算DNA相对含量(DNARC)及增殖指数(PI)。结果与相同时间对照组比较,染毒90 d高浓度氟化钠染毒组大鼠肝细胞S期细胞构成明显增多,差异有统计学意义(P<0.05);且中、高浓度氟化钠染毒组大鼠肝细胞DNARC和PI值成时间依赖性升高(均P<0.05)。各浓度氟化钠染毒组肾细胞周期及各时相细胞数目与对照组相比无明显差异;其中,肾细胞DNARC和PI值在染毒60 d时随氟化钠染毒剂量的增加而显著降低(均P<0.05),在染毒90 d时随氟化钠染毒剂量的升高而呈先上升后下降的趋势(均P>0.05),在染毒120 d时随氟化钠染毒剂量的升高而显著增加(均P<0.05);且高浓度氟化钠染毒组肾细胞DNARC和PI值均高于对照组,差异有统计学意义(P<0.05)。结论过量氟可抑制大鼠肝细胞增殖分化,其机制可能与氟阻滞肝细胞S期进程有关;氟通过干扰肾脏细胞G1/S和G2/M周期进程而诱发肾细胞增殖失控,这可能是氟中毒肾损伤病理变化的重要机制。
Objective To explore the time-effect and dose-effect of fluoride on cell cycle arrest in rat liver and kidney cells. Methods Sixty healthy male SD rats of SPF grade were randomly divided into four groups, 15 rats in each group. The concentration of sodium fluoride for the four groups was 0 mg/L in control group,lO mg/L in low dose fluoride group, 50 mg/L in moderate dose fluoride group and 100 mg/L in high dose fluoride group respectively. The sodium fluoride was administered through drinking water for 120 days. The cell cycle of liver and kidney were determined by flow cytometry（FCM） and the DNARc and PI were measured also. Results Compared with the control group in the same time,the rat liver cells in S phase increased significantly in the high fluoride group at the 90th day of exposure （P〈0.05）, and the DNARc and PI of liver cell in the moderate and high fluoride groups were increased in a significant time-dependent manner （P〈0.05）. Compared with the control group in the same time,there was no significant difference in kidney cell cycle and the cell number in all phases of cell cycle. At the 60th day of the exposure, DNA_Rc and PI of kidney cell decreased significantly in a dose-dependent manner （P〈0.05）,but at the 90th day,the DNARc and PI of kidney cell raised at first and then declined （P〈0.05）. At the 120th day, DNA_RC and PI of kidney cell increased in a dose-dependent manner,the difference in high fluoride was significant （P〈0.05）. Conclusion Excessive fluoride can inhibit liver cell proliferation and differentiation and it may be related with the S phase arrest. Fluoride may induce the loss of control in proliferation of kidney cells by disturbing the G1/S and G2/M phase and this may be the important mechanism of kidney injury in fluoride poisoning.
出处
《环境与健康杂志》
CAS
CSCD
北大核心
2013年第4期317-320,共4页
Journal of Environment and Health
基金
广东省自然科学基金(9151022401000003)
2010年广东药学院大学生创新实验项目
