不同剂量氟对大鼠血管内皮损伤的影响

Effects of different doses of fluoride on vascular endothelial injury in rats

目的探讨不同剂量氟对大鼠血管内皮损伤的影响。方法选取2~3月龄的清洁级雄性SD大鼠30只,体质量为180~220 g,采用饮水染氟法建立大鼠氟中毒模型,按照体质量采用随机数字表法分为对照组(氟化钠含量0 mg/L)、低剂量组(氟化钠含量100 mg/L)、高剂量组(氟化钠含量200 mg/L),每组10只。大鼠持续染氟12周,每隔2周测量体质量。染氟12周后,采用酶联免疫吸附实验(ELISA)检测各组大鼠血清骨钙素(BGP)、内皮素-1(ET-1)、细胞间黏附因子-1(ICAM-1)、白细胞介素-6(IL-6)、脂联素(APN)的含量。透射电镜观察大鼠腹主动脉血管内皮超微结构的改变。结果大鼠染氟第4周,对照组体质量[(306.90±19.13)g]高于低、高剂量组[(280.31±18.44)、(269.03±17.47)g,P均<0.05],但低剂量与高剂量组间比较差异无统计学意义(P>0.05);染氟第6、8、10、12周,对照组体质量[(377.40±23.72)、(422.89±32.23)、(450.00±29.26)、(473.20±28.43)g]高于低、高剂量组[(329.50±21.78)、(368.90±23.79)、(395.17±28.22)、(409.27±29.95)g;(306.75±27.09)、(343.00±18.41)、(362.99±21.77)、(371.76±21.65)g,P均<0.05],且高剂量组体质量低于低剂量组(P均<0.05)。大鼠饮水染氟12周后,对照组血清BGP、ET-1、ICAM-1、IL-6水平均低于低、高剂量组,血清APN高于低、高剂量组(P均<0.05);高剂量组血清BGP、ET-1、ICAM-1、IL-6水平高于低剂量组,APN低于低剂量组(P<0.05);同对照组相比,低剂量组血管内皮细胞外部突体不规范,内皮与基膜连接不紧密,空泡明显;高剂量组内皮细胞连接变短或脱离,胞内异染色质含量明显增多,内皮细胞脱落到血管腔,内皮细胞凋亡。结论高氟可引起大鼠血管内皮损伤。

Objective To investigate the effects of different doses of fluoride on vascular endothelial injury in rats.Methods Thirty clean male SD rats of 2-3 months old were selected,with body mass of 180-220 g.According to body mass,they were divided into three groups by random number table.The rat model of fluorosis was established by drinking water intoxication.According to the concentration of sodium fluoride in drinking water,the three dosage groups were blank control group(0 mg/L of sodium fluoride),low dose group(100 mg/L of sodium fluoride),and high dose group(200 mg/L of sodium fluoride),with 10 rats in each group.The rats were continuously exposed to fluoride for 12 weeks,and their body mass was measured every 2 weeks.After 12 weeks of fluoride exposure,the levels of serum osteocalcin(BGP),endothelin-1(ET-1),intercellular adhesion factor-1(ICAM-1),interleukin-6(IL-6)and adiponectin(APN)were measured by enzyme-linked immunosorbent assay(ELISA).The ultrastructure of vascular endothelium in rats was observed by transmission electron microscopy.Results At the 4th week of fluoride exposure,the body mass of rats in the blank control group was higher than that of the fluoride-exposed groups[(306.90±19.13),(280.31±18.44),(269.03±17.47)g,P<0.05],but there was no significant difference between the low dose group and the high dose group(P>0.05).From the 6th week of fluoride exposure,the body mass of rats in the blank control group was higher than that in the fluoride-exposed groups[(377.40±23.72),(329.50±21.78),(306.75±27.09);(422.89±32.23),(368.90±23.79),(343.00±18.41);(450.00±29.26),(395.17±28.22),(362.99±21.77);(473.20±28.43),(409.27±29.95),(371.76±21.65)g,P<0.05],while that in the high dose group was lower than that in the low dose group(P<0.05).After 12 weeks of fluoride exposure through drinking water,the levels serum BGP,ET-1,ICAM-1 and IL-6 in blank control group were lower than those in fluoride-exposed groups(P<0.05),and the serum APN was higher than that in fluoride-exposed groups(P<0.05);while the levels of serum BGP,ET-1,ICAM-1 and IL-6 in high dose group were higher than those in low dose group,and the level of serum APN was lower than that in low dose group(P<0.05).Compared with the blank control group,the external processes of vascular endothelial cells in the low dose group were not standardized,the endothelial cells were not closely connected with the basement membrane,and the vacuoles were obvious.In the high dose group,the endothelial cells became short or detached;the content of heterochromatin increased significantly,the endothelial cells dropped into the vascular cavity,and with endothelial cells apoptosis.Conclusion High fluoride can cause vascular endothelial injury.