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目的探讨Hedgehog(Hh)信号通路对氟中毒大鼠软骨损害的影响。方法选健康大鼠60只,依据随机数表法分为对照组(自来水)、低氟组(10 mg/L氟化钠溶液)、高氟组(50 mg/L氟化钠溶液),记录不同染氟强度下大鼠软骨细胞活性与凋亡率,比较3组软骨细胞中音速刺猬蛋白(Shh)、印度刺猬蛋白(Ihh)、跨膜蛋白(Smo)、跨膜蛋白受体(Ptch1)、核转录因子蛋白(Gli1、Gli2、Gli3 mRNA)及蛋白表达水平。结果对照组、低氟组、高氟组大鼠软骨细胞活性分别为(100.00±0.00)%、(116.48±10.27)%、(76.25±11.38)%,细胞凋亡率分别为(4.15±0.78)%、(3.02±0.71)%、(9.58±1.14)%。对照组、低氟组、高氟组大鼠软骨细胞Shh、Ihh、Smo、Gli1、Gli2 mRNA表达及Shh、Ihh、Smo、Ptch1、Gli1、Gli2蛋白表达水平依次升高,Gli3 mRNA表达水平逐渐降低(P<0.05),Ptch1 mRNA表达、Gli3蛋白表达在低氟组有所降低,在高氟组略有升高,但差异无统计学意义(P>0.05)。结论氟中毒主要通过Hh信号通路损伤大鼠软骨细胞活性和凋亡,Shh、Ihh、Smo、Ptch1、Gli1、Gli2、Gli3等均参与软骨损伤的活动过程。
Objective To investigate the effect of Hedgehog (Hh) signaling pathway on cartilage damage in fluorosis rats. Methods Sixty healthy rats were randomly divided into control group (tap water), low fluoride group (10 mg / L sodium fluoride solution) and high fluoride group (50 mg / L sodium fluoride solution) according to random number table. The chondrocytes activity and apoptosis rate of rats under different fluoride levels were compared. The sonicated hedgehog (Shh), hedgehog (Ihh), transmembrane protein (Smo), transmembrane protein receptor (Ptch1) , Nuclear transcription factor (Gli1, Gli2, Gli3 mRNA) and protein expression level. Results The chondrocytes in the control group, the low fluoride group and the high fluoride group were (100.00 ± 0.00)%, (116.48 ± 10.27)% and (76.25 ± 11.38)%, respectively. The apoptotic rates were (4.15 ± 0.78) %, (3.02 ± 0.71)%, (9.58 ± 1.14)%. The expressions of Shh, Ihh, Smo, Gli1 and Gli2 mRNA and the expressions of Shh, Ihh, Smo, Ptch1, Gli1 and Gli2 in the control group, the low fluoride group and the high fluoride group increased in turn and the expression of Gli3 mRNA gradually decreased (P <0.05). The expression of Ptch1 mRNA and Gli3 protein in the low fluoride group decreased slightly, but slightly increased in the high fluoride group, but the difference was not statistically significant (P> 0.05). Conclusion Fluorosis can damage the activity and apoptosis of rat chondrocytes mainly through Hh signaling pathway. Shh, Ihh, Smo, Ptch1, Gli1, Gli2 and Gli3 participate in the process of cartilage injury.