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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 study the time-effect and dose-effect of fluoride exposure in drinking water on cell cycle arrest in rat liver and kidney. Methods Sixty healthy SPF male SD rats were randomly divided into four groups: control (distilled water) group and low (10 mg / L), medium (50 mg / L) and high Sodium poisoning group, each group of 15. Adopt free drinking way to carry on poisoning, continuous poisoning 120 d. Flow cytometry was used to detect the cell cycle distribution of liver and kidney, and the relative DNA content (DNARC) and proliferation index (PI) were calculated. Results Compared with the control group at the same time, the hepatocyte S phase cells in the high-concentration sodium fluoride exposure group at 90 d after exposure were significantly increased, the difference was statistically significant (P <0.05); and medium and high concentration of sodium fluoride The DNARC and PI of hepatocytes in the treated group were increased in a time-dependent manner (all P <0.05). There was no significant difference in the number of renal cell cycle and the number of cells in each phase between the sodium fluoride exposure group and the control group. The DNARC and PI values of renal cells increased with the dosage of sodium fluoride (All P <0.05). At the 90th day after exposure, the concentration of sodium fluoride increased first and then decreased (all P> 0.05) (P <0.05). The DNARC and PI of renal cell in high concentration sodium fluoride exposure group were significantly higher than those in control group (P <0.05). Conclusion Excessive fluoride can inhibit the proliferation and differentiation of rat hepatocytes. The mechanism may be related to the S-phase progression of hepatic cells with fluorine. Fluorine may induce uncontrolled proliferation of renal cells by interfering with the G1 / S and G2 / M cycle of kidney cells, which may be Fluorosis poisoning renal injury pathological changes of the important mechanisms.