过量氟暴露对成骨细胞微小染色体维系蛋白3及成骨相关基因表达的影响

Objective To study the effects of fluoride on minichromosone maintenance(MCM)3 mRNA and the bone formation-related gene:bone sialoprotein(BSP),osteocalcin(OC),osteopontin(OP)mRNA expression on human osteoblast cells.The expression of MCM3 was tested for diagnosis and surveillance value on osteoblast treated with excess fluoride.Methods Human osteoblast cell(Saos-2)was cultured in McCoy5A medium and treated with fluoride(sodium fluoride,NaF).There were eight groups including:0(control),0.625,1.250,2.500,5.000,10.000,20.000,40.000 mg/L groups.Expression of MCM3,BSP,OC,OP mRNA were detected by real-time PCR.Dual-standard curve method was used for analysis.ALPase was determined by measuring the absorbance using a micro titer plate reader. Results Expression of MCM3 mRNA was lower in the 0.625,1.250,2.500,5.000,20.000, 40.000 mg/L groups(0.059 ± 0.003,0.027 ± 0.001,0.272 ± 0.004,0.115 ± 0.002,0.137 ± 0.004,0.754 ±0.002, all P > 0.05) and was higher in10.000 mg/L group(21.300 ± 1.200, P < 0.01 ) than control group( 1.000 ±0.020), especially 10.000 mg/L group was higher than groups treated with fluoride(all P < 0.01 ), the differences among groups were significant(F = 305.842, P < 0.01 ). Expression of BSP mRNA was significantly higher in 0.625,1.250,2.500,5.000,10.000 mg/L groups(71.80 ± 3.60,133.00 ± 7.20,85.50 ± 0.60,80.90 ± 1.20,304.00 ± 21.00)than the control group( 1.00 ± 0.04), especially 10.000 mg/L group was higher than others groups treated with fluoride(all P < 0.01 ), the differences among groups were signifieant(F = 159.531, P < 0.01 ). Expressions of OC mRNA were higher in 0.625,1.250,2.500,5.000 mg/L groups(110.00 ± 12.00,143.00 ± 2.10,90.60 ± 4.10,23.70±1.20) than control group(1.00 ± 0.01, all P < 0.01), and the differences among groups were significant (F = 158.734, P < 0.01 ). Expression of OP mRNA were higher in 0.625,1.250,2.500,5.000,10.000,20.000 mg/L groups(167.00 ± 11.20, 111.00 ± 12.10,72.50 ± 3.50,134.00 ± 14.00,42.30 ± 2.40,45.20 ± 3.30) than the control group(1.00 ± 0.04, all P < 0.05 or < 0.01 ), the differences among groups were significant(F = 60.226, P < 0.01 ).Compared with control group(4.2 ± 1.2), the ALPase activity was increased in all groups treated with fluoride (6.0 ± 0.4,5.8 ± 0.1,5.7 ± 0.4,7.7 ± 1.1,19.2 ± 2.4,8.5 ± 3.0,18.1 ± 4.2), but only 10.000 mg/L and 40.000 mg/L groups were higher than control group and other groups treated with fluoride(all P < 0.01 ), the differences among groups were signifieant(F = 7.806, P < 0.01 ). Conclusions Irregular expression of MCM3 mRNA is not suitable as a diagnostic and monitoring biomarker of osteoblasts exposed to excessive fluoride. Fluoride may affect the osteoblast-related gene expression and to promote osteogenic differentiation.     

氟对大鼠骨代谢的影响

Objective To study the effect of fluoride on bone metabolism in rats, and to understand the mechanism of pathogenesis of skeletal fluorosis. Methods A total of 80 Wistar rats were randomly divided into 4 groups that included control group (distilled water), low-dose group(NaF, 50 mg/L), medium-dose group (NaF,100 mg/L) and high-dose group(NaF, 150 mg/L), respectively. After being bred for 12 weeks, the rats were put to death (etherization). Incidence of dental fluorosis was estimated, and serum was collected. Radioimmunoassay was employed to detect the levels of osteocalcin (BGP), parathyroid hormone (PTH) and calcitonin (CT), respectively.Colorimetry method was employed to determine the levels of alkaline phosphatase (ALP) and acid phosphatase (ACP). Results Incidence of dental fluorosis between the four groups was significantly different statistically(x2 =82.81 ,P ＜ 0.01 ). The incidence was significantly different(x2 = 22.67, 40.00, 40.00, all P＜ 0.01 ) between low-dose ( 80%, 16/20), medium-dose ( 100%, 20/20), high-dose groups ( 100%, 20/20) and control group (0,0/20),respectively. Serum levels of BGP, PTH, CT were significantly different between the groups(F = 38.614, 20.778,3.023, P ＜ 0.01 or ＜ 0.05). There was no significant difference between the four.groups of ALP and ACP in serum (F = 0.609,2.895, all P ＞ 0.05 ). Serum BGP in low-dose, medium-dose and high-dose groups[ ( 19.60 ± 12.79),(33.41 ± 10.81 ), (39.46 ± 9.51 )mg/L, respectively] was significantly higher than that of the control group[ (7.35 ± 3.22)mg/L, all P ＜ 0.01 ]. Serum PTH in low-dose, medium-dose and high-dose groups[ (72.27 ± 25.38), (67.80 ± 12.01), (106.52 ± 36.37)pmol/L] was significantly higher than that of the control group[(47.08 ± 9.22)pmol/L,all P ＜ 0.01 ]. Serum PTH of the high-dose group was significantly higher than that of the low-dose and the mediumdose groups(all P ＜ 0.01 ). Serum CT in medium-dose and high-dose groups[ ( 13.39 ± 2.07), ( 15.05 ± 4.77)pmol/L ] was significantly lower than that of the control group[ (26.06 ± 28.31 ) pmol/L, all P ＜ 0.05 ] and also significantly lower than that of the low-dose group [ (24.49 ± 14. 10) pmol/L, all P ＜ 0.05 ]. Conclusions Fluoride affects bone metabolism in rats, BGP, PTH and CT play a key role in the pathogenesis of skeletal fluorosis.     

硒对高氟所致兔血管内皮损伤及动脉硬化影响的病理形态学研究

Objective To study morphological changes of rabbit artery endothelial cell injury and atherosclerosis caused by high fluoride and the role of selenium. Methods Twenty healthy male New Zealand white rabbits, body weight (2.0 ± 0.5)kg, were randomly divided into control group(drinking deionized water, fed basic diet), fluoride group(drinking fluoride 100 mg/L deionized water, fed basic diet), selenium group(drinking selenium 1 mg/L deionized water, fed basic diet), fluoride plus selenium group(drinking fluoride 100 mg/L deionized water, selenium 1 mg/L of deionized water, fed basic diet). The experimental period was 6 months. At 0, 3, 6 months of the experiment, serum fluorine and selenium levels were determined. At the end of the experiment,thoracic aorta was collected to observe its pathology and ultrastructural changes. Results Serum fluoride was significantly higher at the 3rd and the 6th month of experiment(all P ＜ 0.01 ) in fluoride group[ (0.589 ± 0.146),(0.772 ± 0.175)mg/L] and fluoride plus selenium group[ (0.502 ± 0.094), (0.693 ± 0.158)mg/L] than in control group[ (0.174 ± 0.002), (0.208 ± 0.031 )mg/L] and serum fluoride was significantly higher at 6 months than at 3 months(P ＜ 0.05 ) in fluoride group. Serum selenium was significantly higher at the 3rd and the 6th month of experiment (all P ＜ 0.01 ) in selenium group[ (0.252 ± 0.022), (0.319 ± 0.052)mg/L] and fluoride plus selenium group[ (0.239 ±0.016), (0.294 ± 0.018)mg/L] than in control group[(0.135 ± 0.014), (0.167 ± 0.019)mg/L], and serum selenium was significantly higher at the 6th month than at 3rd month of experiment in selenium group(P ＜ 0.05). Endothelial cell apoptosis indices were (4.92 ± 1.32)%, (30.30 ± 6.80)%, (6.57 ± 2.14)% and (14.29 ± 2.99)%, respectively in control group, fluoride group, selenium group and fluoride plus selenium group. Their main effect of fluorine and selenium was statistically significant (F = 106.833,20.082, all P ＜ 0.01 ). There were antagonistic effect between fluoride and selenium(F = 30.402, P ＜ 0.01 ). Pathological changes of rabbit aortic endothelial cells in fluoride group included endothelial with attached fibrin and red blood cells, and structural of the cells changed, with serious vascular injury; in fluoride plus selenium group apoptosis of endothelial cells decreased, with reduced number of attached red blood cells and fibrin, endothelial cell structure normal, the extent and scope of vascular damage significantly reduced. Conclusions Appropriate amount of selenium inhibits the apoptosis of endothelial cells induced by high fluoride, reduces aortic structural damage caused by high fluoride, and maintains the integrity of endothelial cells, thereby antagonizes the vascular damage and atherosclerosis induced by high fluoride.     

慢性氟中毒大鼠脑组织中c-Jun氨基末端激酶表达水平观察

Objective To investigate the expression of c-Jun-N-terminal kinase(JNK) in rat brains with chronic fluorosis and try to reveal the molecular mechanism for the neural impairment induced by the disease.Methods The rats were randomly divided into 3 groups, normal control group(drinking water containing less than 0.5 mg/L of sodium fluoride, NaF), lower fluoride exposed group(drinking water containing 5 mg/L NaF) and higher fluoride exposed group(drinking water containing 50 mg/L NaF), 24 in every group. The rats were examined at the sixth month after feeding. The concentration of fluorine in urine and blood was detected by F-ion selective electrode. The expression of JNK in brains was investigated by using Western blotting and immunohitochemistry staining, and analyze the correlation between activating of JNK and the concentration of fluorine in blood. Results The increased concentration of fluorine in urine(control: 0.92 ± 0.30, lower fluoride exposed group: 2.56 ± 0.91,higher fluoride exposed group: 5.73 ± 3.14, P ＜ 0.05) were observed when 6 months after the beginning of the experiment, and the amount of fluorine in blood was also higher in rats with fluorosis(control: 0.12 ± 0.07, lower fluoride exposed group: 0.36 ± 0.14, higher fluoride exposed group: 0.50 ± 0.18, P ＜ 0.05). The expression of phospho-JNK at protein levels were higher in the brains of rats with fluorosis than that of controls (control: 1.00 ± 0.37, lower fluoride exposed group: 1.20 ± 0.28, higher fluoride exposed group: 1.74 ± 0.69, P ＜ 0.05), whereas no change of total-JNK was found(F = 0.046, P ＞ 0.05). Furthermore, the expression of phospho-JNK in the parietal cortex(119.3 ± 14.1), occipital cortex(112.7 ± 5.4), hippocampus CA3(100.6 ± 8.9), dorsal thalamus (117.8 ± 10.4) and olivary nucleus( 112.6 ± 5.9) of rats in higher fluoride exposed group were higher than that in control( 104.1 ± 8.9,106.6 ± 9.6,106.6 ± 9.7,108.9 ± 6.4,100.3 ± 8.4, all P ＜ 0.05) and lower fluoride exposed group(96.7 ± 17.1,102.5 ± 8.3,106.4 ± 6.5,110.2 ± 9.3,102.4 ± 4.7,102.5 ± 9.8, all P＜ 0.05). The positive stained neurons of total-JNK also distributed in the same brain regions of rats, but no difference was detected between the rats with fluorosis and controls(all P ＞ 0.05). The increased level of phospho-JNK was positively correlated with the fluoride contents in blood of the rats with fluorosis (r = 0.677). Conclusions The expression of phospho-JNK in brains of rats with fluorosis was significantly increased with a correlation to fluoride content in blood, which might be connected to the mechanism of neural impairment induced by chronic fluorosis.     

碘过量对NOD和Balb/c鼠甲状腺TRAIL和TRAIL-sR1表达的影响

Objective To investigate the influence of iodine excess on expression of TRAIl/TRAIL-sR1 in NOD and Balb/c mice and to study the effect of TRAIl/TRAIL-sR1 on the pathogenesis of experimental autoimmune thyroiditis(EAT). Methods Both Balb/c and NOD mice were divided randomly into control and iodine excess group by feeding with water containing no NaI or 0.05% Nal. The mice were sacrificed after 8 weeks. TRAIL and TRAIL-sR1 mRNA levels were detected by RT-PCR. The function, morphology and apoptosis of thyroids were also observed by ELISA and Tunnel stain. Results Treated by HI, enlarged follicles and flattened epithelium by accumulation of colloid were found in thyroids of both NOD and Balb/c mice. But significant lymphoid cell infiltration and local fibrosis were only found in thyroids of NOD HI group. The relative weight of thyroids of NOD mice in HI group[(104.8±14.5)mg/kg]was heavier than that of control group [(71.8±20.4)mg/kg]. The level of TT4 declined in HI group[(30.77±3.59)mmol/L]compared with control group[(36.43±2.66)mmol/L], meanwhile, the level of TSH was higher in HI group[(6.98±0.66)μg/L]than that in control group [(5.55±0.56)μg/L]. The difference being statistically significant(t=7.773,-9.526,-4.458, all P < 0.05). The relative weight of thyroids of Balb/c mice of HI group[(155.8±20.8)mg/kg]also heavier than that of control group [(105.1±22.0) mg/kg]. The level of TT4 droped in HI group [(19.75±3.32) mmoL/L]was higher than that in control group[(23.46±6.21)mmoL/L], the level of TSH in HI group[(4.14±1.71)μg/L]was higher than that in control group[(3.55±1.41)μg/L], the difference being statistically significant(t=7.554,-7.239,3.140, all P< 0.05). A great deal of apoptotie ceils observed in NOD (3.97±0.91) and Balb/c mice (1.05±0.45) by Tunnel stain were greater than control groups (0.21±0.15, 0.10±0.03), the difference being statistically significant in beth of the two species(t=-7.167,-17.772, both P < 0.05). The apoptosis index of thyroid follicular epithelium in NOD was obviously higher than Balb/c(t=-7.625, P<0.05). The level of TRAIL mRNA did not remarkably change in Balb/c between control group(0.000 59±0.000 39) and HI group(0.001 24±0.000 46, t=-1.940, P>0.05), but it increased apparently in NOD mice HI group(0.018 88±0.005 77) than that of control group(0.009 61± 0.00591, t=-2.71, P<0.05). The level of the expression of TRAIL-sR1 mRNA increased in HI groups of NOD (0.000 53±0.000 15) and Balb/c mice(0.000 42±0.000 09) than that in control groups of NOD(0.000 28± 0.000 05) and Balb/c mice (0.000 17±0.000 06) and the differences were statistically significant between the two species(t=3.050,3.990, all P<0.05). The differences of the expression of TRAIL and TRAIL-sR1 mRNA between the two species were significant(t=-3.37,-4.76, all P<0.05). Conclusions Iodine excess induces colloid goiter in beth species of mice and thyroiditis in NOD mice. The increase of TRAIL and TRAIL-sR1 influenced by iodine excess is one of the molecular bases of follicular epithelium apoptosis and inflammation in thyroids. Genetic factor is a key factor in the pathogenesis of thyroiditis.     

碘过量对NOD和Balb/c鼠甲状腺TRAIL和TRAIL-sR1表达的影响

Objective To investigate the influence of iodine excess on expression of TRAIl/TRAIL-sR1 in NOD and Balb/c mice and to study the effect of TRAIl/TRAIL-sR1 on the pathogenesis of experimental autoimmune thyroiditis(EAT). Methods Both Balb/c and NOD mice were divided randomly into control and iodine excess group by feeding with water containing no NaI or 0.05% Nal. The mice were sacrificed after 8 weeks. TRAIL and TRAIL-sR1 mRNA levels were detected by RT-PCR. The function, morphology and apoptosis of thyroids were also observed by ELISA and Tunnel stain. Results Treated by HI, enlarged follicles and flattened epithelium by accumulation of colloid were found in thyroids of both NOD and Balb/c mice. But significant lymphoid cell infiltration and local fibrosis were only found in thyroids of NOD HI group. The relative weight of thyroids of NOD mice in HI group[(104.8±14.5)mg/kg]was heavier than that of control group [(71.8±20.4)mg/kg]. The level of TT4 declined in HI group[(30.77±3.59)mmol/L]compared with control group[(36.43±2.66)mmol/L], meanwhile, the level of TSH was higher in HI group[(6.98±0.66)μg/L]than that in control group [(5.55±0.56)μg/L]. The difference being statistically significant(t=7.773,-9.526,-4.458, all P < 0.05). The relative weight of thyroids of Balb/c mice of HI group[(155.8±20.8)mg/kg]also heavier than that of control group [(105.1±22.0) mg/kg]. The level of TT4 droped in HI group [(19.75±3.32) mmoL/L]was higher than that in control group[(23.46±6.21)mmoL/L], the level of TSH in HI group[(4.14±1.71)μg/L]was higher than that in control group[(3.55±1.41)μg/L], the difference being statistically significant(t=7.554,-7.239,3.140, all P< 0.05). A great deal of apoptotie ceils observed in NOD (3.97±0.91) and Balb/c mice (1.05±0.45) by Tunnel stain were greater than control groups (0.21±0.15, 0.10±0.03), the difference being statistically significant in beth of the two species(t=-7.167,-17.772, both P < 0.05). The apoptosis index of thyroid follicular epithelium in NOD was obviously higher than Balb/c(t=-7.625, P<0.05). The level of TRAIL mRNA did not remarkably change in Balb/c between control group(0.000 59±0.000 39) and HI group(0.001 24±0.000 46, t=-1.940, P>0.05), but it increased apparently in NOD mice HI group(0.018 88±0.005 77) than that of control group(0.009 61± 0.00591, t=-2.71, P<0.05). The level of the expression of TRAIL-sR1 mRNA increased in HI groups of NOD (0.000 53±0.000 15) and Balb/c mice(0.000 42±0.000 09) than that in control groups of NOD(0.000 28± 0.000 05) and Balb/c mice (0.000 17±0.000 06) and the differences were statistically significant between the two species(t=3.050,3.990, all P<0.05). The differences of the expression of TRAIL and TRAIL-sR1 mRNA between the two species were significant(t=-3.37,-4.76, all P<0.05). Conclusions Iodine excess induces colloid goiter in beth species of mice and thyroiditis in NOD mice. The increase of TRAIL and TRAIL-sR1 influenced by iodine excess is one of the molecular bases of follicular epithelium apoptosis and inflammation in thyroids. Genetic factor is a key factor in the pathogenesis of thyroiditis.     

碘过量对NOD和Balb/c鼠甲状腺TRAIL和TRAIL-sR1表达的影响

Objective To investigate the influence of iodine excess on expression of TRAIl/TRAIL-sR1 in NOD and Balb/c mice and to study the effect of TRAIl/TRAIL-sR1 on the pathogenesis of experimental autoimmune thyroiditis(EAT). Methods Both Balb/c and NOD mice were divided randomly into control and iodine excess group by feeding with water containing no NaI or 0.05% Nal. The mice were sacrificed after 8 weeks. TRAIL and TRAIL-sR1 mRNA levels were detected by RT-PCR. The function, morphology and apoptosis of thyroids were also observed by ELISA and Tunnel stain. Results Treated by HI, enlarged follicles and flattened epithelium by accumulation of colloid were found in thyroids of both NOD and Balb/c mice. But significant lymphoid cell infiltration and local fibrosis were only found in thyroids of NOD HI group. The relative weight of thyroids of NOD mice in HI group[(104.8±14.5)mg/kg]was heavier than that of control group [(71.8±20.4)mg/kg]. The level of TT4 declined in HI group[(30.77±3.59)mmol/L]compared with control group[(36.43±2.66)mmol/L], meanwhile, the level of TSH was higher in HI group[(6.98±0.66)μg/L]than that in control group [(5.55±0.56)μg/L]. The difference being statistically significant(t=7.773,-9.526,-4.458, all P < 0.05). The relative weight of thyroids of Balb/c mice of HI group[(155.8±20.8)mg/kg]also heavier than that of control group [(105.1±22.0) mg/kg]. The level of TT4 droped in HI group [(19.75±3.32) mmoL/L]was higher than that in control group[(23.46±6.21)mmoL/L], the level of TSH in HI group[(4.14±1.71)μg/L]was higher than that in control group[(3.55±1.41)μg/L], the difference being statistically significant(t=7.554,-7.239,3.140, all P< 0.05). A great deal of apoptotie ceils observed in NOD (3.97±0.91) and Balb/c mice (1.05±0.45) by Tunnel stain were greater than control groups (0.21±0.15, 0.10±0.03), the difference being statistically significant in beth of the two species(t=-7.167,-17.772, both P < 0.05). The apoptosis index of thyroid follicular epithelium in NOD was obviously higher than Balb/c(t=-7.625, P<0.05). The level of TRAIL mRNA did not remarkably change in Balb/c between control group(0.000 59±0.000 39) and HI group(0.001 24±0.000 46, t=-1.940, P>0.05), but it increased apparently in NOD mice HI group(0.018 88±0.005 77) than that of control group(0.009 61± 0.00591, t=-2.71, P<0.05). The level of the expression of TRAIL-sR1 mRNA increased in HI groups of NOD (0.000 53±0.000 15) and Balb/c mice(0.000 42±0.000 09) than that in control groups of NOD(0.000 28± 0.000 05) and Balb/c mice (0.000 17±0.000 06) and the differences were statistically significant between the two species(t=3.050,3.990, all P<0.05). The differences of the expression of TRAIL and TRAIL-sR1 mRNA between the two species were significant(t=-3.37,-4.76, all P<0.05). Conclusions Iodine excess induces colloid goiter in beth species of mice and thyroiditis in NOD mice. The increase of TRAIL and TRAIL-sR1 influenced by iodine excess is one of the molecular bases of follicular epithelium apoptosis and inflammation in thyroids. Genetic factor is a key factor in the pathogenesis of thyroiditis.     

碘过量对NOD和Balb/c鼠甲状腺TRAIL和TRAIL-sR1表达的影响

Objective To investigate the influence of iodine excess on expression of TRAIl/TRAIL-sR1 in NOD and Balb/c mice and to study the effect of TRAIl/TRAIL-sR1 on the pathogenesis of experimental autoimmune thyroiditis(EAT). Methods Both Balb/c and NOD mice were divided randomly into control and iodine excess group by feeding with water containing no NaI or 0.05% Nal. The mice were sacrificed after 8 weeks. TRAIL and TRAIL-sR1 mRNA levels were detected by RT-PCR. The function, morphology and apoptosis of thyroids were also observed by ELISA and Tunnel stain. Results Treated by HI, enlarged follicles and flattened epithelium by accumulation of colloid were found in thyroids of both NOD and Balb/c mice. But significant lymphoid cell infiltration and local fibrosis were only found in thyroids of NOD HI group. The relative weight of thyroids of NOD mice in HI group[(104.8±14.5)mg/kg]was heavier than that of control group [(71.8±20.4)mg/kg]. The level of TT4 declined in HI group[(30.77±3.59)mmol/L]compared with control group[(36.43±2.66)mmol/L], meanwhile, the level of TSH was higher in HI group[(6.98±0.66)μg/L]than that in control group [(5.55±0.56)μg/L]. The difference being statistically significant(t=7.773,-9.526,-4.458, all P < 0.05). The relative weight of thyroids of Balb/c mice of HI group[(155.8±20.8)mg/kg]also heavier than that of control group [(105.1±22.0) mg/kg]. The level of TT4 droped in HI group [(19.75±3.32) mmoL/L]was higher than that in control group[(23.46±6.21)mmoL/L], the level of TSH in HI group[(4.14±1.71)μg/L]was higher than that in control group[(3.55±1.41)μg/L], the difference being statistically significant(t=7.554,-7.239,3.140, all P< 0.05). A great deal of apoptotie ceils observed in NOD (3.97±0.91) and Balb/c mice (1.05±0.45) by Tunnel stain were greater than control groups (0.21±0.15, 0.10±0.03), the difference being statistically significant in beth of the two species(t=-7.167,-17.772, both P < 0.05). The apoptosis index of thyroid follicular epithelium in NOD was obviously higher than Balb/c(t=-7.625, P<0.05). The level of TRAIL mRNA did not remarkably change in Balb/c between control group(0.000 59±0.000 39) and HI group(0.001 24±0.000 46, t=-1.940, P>0.05), but it increased apparently in NOD mice HI group(0.018 88±0.005 77) than that of control group(0.009 61± 0.00591, t=-2.71, P<0.05). The level of the expression of TRAIL-sR1 mRNA increased in HI groups of NOD (0.000 53±0.000 15) and Balb/c mice(0.000 42±0.000 09) than that in control groups of NOD(0.000 28± 0.000 05) and Balb/c mice (0.000 17±0.000 06) and the differences were statistically significant between the two species(t=3.050,3.990, all P<0.05). The differences of the expression of TRAIL and TRAIL-sR1 mRNA between the two species were significant(t=-3.37,-4.76, all P<0.05). Conclusions Iodine excess induces colloid goiter in beth species of mice and thyroiditis in NOD mice. The increase of TRAIL and TRAIL-sR1 influenced by iodine excess is one of the molecular bases of follicular epithelium apoptosis and inflammation in thyroids. Genetic factor is a key factor in the pathogenesis of thyroiditis.     

碘过量对NOD和Balb/c鼠甲状腺TRAIL和TRAIL-sR1表达的影响

Objective To investigate the influence of iodine excess on expression of TRAIl/TRAIL-sR1 in NOD and Balb/c mice and to study the effect of TRAIl/TRAIL-sR1 on the pathogenesis of experimental autoimmune thyroiditis(EAT). Methods Both Balb/c and NOD mice were divided randomly into control and iodine excess group by feeding with water containing no NaI or 0.05% Nal. The mice were sacrificed after 8 weeks. TRAIL and TRAIL-sR1 mRNA levels were detected by RT-PCR. The function, morphology and apoptosis of thyroids were also observed by ELISA and Tunnel stain. Results Treated by HI, enlarged follicles and flattened epithelium by accumulation of colloid were found in thyroids of both NOD and Balb/c mice. But significant lymphoid cell infiltration and local fibrosis were only found in thyroids of NOD HI group. The relative weight of thyroids of NOD mice in HI group[(104.8±14.5)mg/kg]was heavier than that of control group [(71.8±20.4)mg/kg]. The level of TT4 declined in HI group[(30.77±3.59)mmol/L]compared with control group[(36.43±2.66)mmol/L], meanwhile, the level of TSH was higher in HI group[(6.98±0.66)μg/L]than that in control group [(5.55±0.56)μg/L]. The difference being statistically significant(t=7.773,-9.526,-4.458, all P < 0.05). The relative weight of thyroids of Balb/c mice of HI group[(155.8±20.8)mg/kg]also heavier than that of control group [(105.1±22.0) mg/kg]. The level of TT4 droped in HI group [(19.75±3.32) mmoL/L]was higher than that in control group[(23.46±6.21)mmoL/L], the level of TSH in HI group[(4.14±1.71)μg/L]was higher than that in control group[(3.55±1.41)μg/L], the difference being statistically significant(t=7.554,-7.239,3.140, all P< 0.05). A great deal of apoptotie ceils observed in NOD (3.97±0.91) and Balb/c mice (1.05±0.45) by Tunnel stain were greater than control groups (0.21±0.15, 0.10±0.03), the difference being statistically significant in beth of the two species(t=-7.167,-17.772, both P < 0.05). The apoptosis index of thyroid follicular epithelium in NOD was obviously higher than Balb/c(t=-7.625, P<0.05). The level of TRAIL mRNA did not remarkably change in Balb/c between control group(0.000 59±0.000 39) and HI group(0.001 24±0.000 46, t=-1.940, P>0.05), but it increased apparently in NOD mice HI group(0.018 88±0.005 77) than that of control group(0.009 61± 0.00591, t=-2.71, P<0.05). The level of the expression of TRAIL-sR1 mRNA increased in HI groups of NOD (0.000 53±0.000 15) and Balb/c mice(0.000 42±0.000 09) than that in control groups of NOD(0.000 28± 0.000 05) and Balb/c mice (0.000 17±0.000 06) and the differences were statistically significant between the two species(t=3.050,3.990, all P<0.05). The differences of the expression of TRAIL and TRAIL-sR1 mRNA between the two species were significant(t=-3.37,-4.76, all P<0.05). Conclusions Iodine excess induces colloid goiter in beth species of mice and thyroiditis in NOD mice. The increase of TRAIL and TRAIL-sR1 influenced by iodine excess is one of the molecular bases of follicular epithelium apoptosis and inflammation in thyroids. Genetic factor is a key factor in the pathogenesis of thyroiditis.     

碘过量对NOD和Balb/c鼠甲状腺TRAIL和TRAIL-sR1表达的影响

Objective To investigate the influence of iodine excess on expression of TRAIl/TRAIL-sR1 in NOD and Balb/c mice and to study the effect of TRAIl/TRAIL-sR1 on the pathogenesis of experimental autoimmune thyroiditis(EAT). Methods Both Balb/c and NOD mice were divided randomly into control and iodine excess group by feeding with water containing no NaI or 0.05% Nal. The mice were sacrificed after 8 weeks. TRAIL and TRAIL-sR1 mRNA levels were detected by RT-PCR. The function, morphology and apoptosis of thyroids were also observed by ELISA and Tunnel stain. Results Treated by HI, enlarged follicles and flattened epithelium by accumulation of colloid were found in thyroids of both NOD and Balb/c mice. But significant lymphoid cell infiltration and local fibrosis were only found in thyroids of NOD HI group. The relative weight of thyroids of NOD mice in HI group[(104.8±14.5)mg/kg]was heavier than that of control group [(71.8±20.4)mg/kg]. The level of TT4 declined in HI group[(30.77±3.59)mmol/L]compared with control group[(36.43±2.66)mmol/L], meanwhile, the level of TSH was higher in HI group[(6.98±0.66)μg/L]than that in control group [(5.55±0.56)μg/L]. The difference being statistically significant(t=7.773,-9.526,-4.458, all P < 0.05). The relative weight of thyroids of Balb/c mice of HI group[(155.8±20.8)mg/kg]also heavier than that of control group [(105.1±22.0) mg/kg]. The level of TT4 droped in HI group [(19.75±3.32) mmoL/L]was higher than that in control group[(23.46±6.21)mmoL/L], the level of TSH in HI group[(4.14±1.71)μg/L]was higher than that in control group[(3.55±1.41)μg/L], the difference being statistically significant(t=7.554,-7.239,3.140, all P< 0.05). A great deal of apoptotie ceils observed in NOD (3.97±0.91) and Balb/c mice (1.05±0.45) by Tunnel stain were greater than control groups (0.21±0.15, 0.10±0.03), the difference being statistically significant in beth of the two species(t=-7.167,-17.772, both P < 0.05). The apoptosis index of thyroid follicular epithelium in NOD was obviously higher than Balb/c(t=-7.625, P<0.05). The level of TRAIL mRNA did not remarkably change in Balb/c between control group(0.000 59±0.000 39) and HI group(0.001 24±0.000 46, t=-1.940, P>0.05), but it increased apparently in NOD mice HI group(0.018 88±0.005 77) than that of control group(0.009 61± 0.00591, t=-2.71, P<0.05). The level of the expression of TRAIL-sR1 mRNA increased in HI groups of NOD (0.000 53±0.000 15) and Balb/c mice(0.000 42±0.000 09) than that in control groups of NOD(0.000 28± 0.000 05) and Balb/c mice (0.000 17±0.000 06) and the differences were statistically significant between the two species(t=3.050,3.990, all P<0.05). The differences of the expression of TRAIL and TRAIL-sR1 mRNA between the two species were significant(t=-3.37,-4.76, all P<0.05). Conclusions Iodine excess induces colloid goiter in beth species of mice and thyroiditis in NOD mice. The increase of TRAIL and TRAIL-sR1 influenced by iodine excess is one of the molecular bases of follicular epithelium apoptosis and inflammation in thyroids. Genetic factor is a key factor in the pathogenesis of thyroiditis.