Zhao Lina, Yu Yanni, Deng Chaonan
Department of Pathology, Guiyang Medical College, Guiyang 550004, China.
Department of Pathology, Guiyang Medical College, Guiyang 550004, China. E-mail:
Zhonghua Bing Li Xue Za Zhi. 2014 Dec;43(12):814-9.
To investigate the expression of sonic hedgehog (Shh) signaling pathway in liver fluorosis and to explore related mechanism.
To establish animal model, 48 normal SD rats (aged 4-5 weeks) were randomly divided into 4 groups (12 each): control group, fluoriosis group, blocking group and blocking control group. After 6 months, the blocking group and blocking control group were injected intraperitoneally once every 2 days for 3 times with 10 mg/kg cyclopamine or dimethysulfoxide, respectively. Rats were sacrificed at the end of the experiment and the fluoride content in urine and liver function was determined. The expression of Shh and Gli1 protein and mRNA in hepatocytes was detected by immunohistochemistry and real-time fluorescence quantitative PCR, respectively.
The fluoride contents in the urine and the incidence of dental fluorosis increased in the fluoride and blocking control groups as compared with those in the control group, but decreased in the blocking group compared with those of the fluoride and blocking control group. Compared with the control group, the titers of aspartate transaminase (AST) and alanine transaminase (ALT) significantly increased, while the activity of total protein and albumin decreased in the fluoride and blocking control groups. Compared with the fluoride and blocking control groups, the activity of the ALT slightly declined and the AST, total protein and albumin slightly increased in the blocking group. Histologically, the cells were disorganized and swollen with cytoplasmic clearing (balloon cells), compared with the control group. The expression of Shh and Gli1 significantly increased in all but the control group. Compared with the fluoride and blocking control groups, the expression of Shh and Gli1 declined in the blocking group.
The overexpression and cyclopamine inhibition of the Shh signaling pathway are closely related to the content of fluoride in the liver. The Shh signaling pathway plays an important role in the pathogenesis of liver injury caused by fluorosis, suggesting a preventive and therapeutic target of the disease.
探讨音猬因子（Shh）信号通路在肝脏氟中毒中的表达情况，并探究其相关机制。
为建立动物模型，将48只4 - 5周龄的正常SD大鼠随机分为4组（每组12只）：对照组、氟中毒组、阻断组和阻断对照组。6个月后，阻断组和阻断对照组分别每2天腹腔注射1次，共注射3次，阻断组注射10 mg/kg环杷明，阻断对照组注射二甲基亚砜。实验结束时处死大鼠，测定尿氟含量及肝功能。分别采用免疫组织化学和实时荧光定量PCR检测肝细胞中Shh和Gli1蛋白及mRNA的表达。
与对照组相比，氟中毒组和阻断对照组尿氟含量及氟斑牙发生率升高，但阻断组与氟中毒组和阻断对照组相比降低。与对照组相比，氟中毒组和阻断对照组天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平显著升高，而总蛋白和白蛋白活性降低。与氟中毒组和阻断对照组相比，阻断组ALT活性略有下降，AST、总蛋白和白蛋白略有升高。组织学检查显示，与对照组相比，细胞排列紊乱、肿胀，细胞质清亮（气球样细胞）。除对照组外，其他组Shh和Gli1的表达均显著增加。与氟中毒组和阻断对照组相比，阻断组Shh和Gli1的表达降低。
Shh信号通路的过表达及环杷明抑制与肝脏氟含量密切相关。Shh信号通路在氟中毒所致肝损伤的发病机制中起重要作用，提示其为该疾病的防治靶点。
