ABSTRACT
Objective:To explore whether chronic fluorosis can cause liver fibrosis in rats by observing expression changes in type Ⅰcollagen (Col-Ⅰ), type Ⅲ collagen (Col-Ⅲ) and alpha smooth actin (α-SMA) in the liver tissue of chronic fluorosis rats.Methods:According to body weight (90 - 100 g), forty-eight SD rats were randomly divided into control group (drinking water fluoride ion concentration < 0.5 mg/L), low, medium and high concentration fluoride groups (drinking water fluoride ion concentration of 5.0, 50.0 and 100.0 mg/L), with 12 rats in each group (half male and half female), and fed for 6 months. Fluoride ion selective electrode method was used to detect bone fluoride and urinary fluoride levels; hematoxylin-eosin staining (HE staining) and Masson staining were used to observe the pathological and morphological changes and the collagen deposition of liver tissue; quantitative real-time polymerase chain reaction and immunohistochemical staining were used to observe Col-Ⅰ, Col-Ⅲ and α-SMA mRNA and protein expressions.Results:There was significant difference in bone fluoride and urine fluoride between the 4 groups [bone fluoride: (92.52 ± 5.64), (112.21 ± 11.86), (142.99 ± 7.87), (235.63 ± 11.55) mg/kg; urinary fluoride: (5.47 ± 0.88), (17.78 ± 1.48), (54.16 ± 5.96), (121.11 ± 6.32) mg/L, P < 0.001]. Under light microscope, with the increase of fluoride concentration, the degree of hepatic cell edema was aggravated, and the deposition of collagen fiber around the central vein and the portal area increased significantly. The mRNA expression level of Col-Ⅰ in low, medium and high concentration fluoride groups (1.20 ± 0.09, 1.80 ± 0.08, 1.58 ± 0.06) was significantly higher than that in control group (1.00 ± 0.00, P < 0.05); Col-Ⅲ and α-SMA mRNA expression levels in medium and high concentration fluoride groups (Col-Ⅲ: 1.15 ± 0.14, 1.64 ± 0.24; α-SMA: 1.69 ± 0.02, 2.34 ± 0.06) were significantly higher than those of low concentration fluoride group (Col-Ⅲ: 0.59 ± 0.17; α-SMA: 0.80 ± 0.13, P < 0.05). With the increase of fluoride concentration, the liver tissue Col-Ⅰ(0.00 ± 0.00, 0.03 ± 0.01, 0.08 ± 0.01, 0.13 ± 0.02), Col-Ⅲ (17 803.05 ± 3 221.16, 47 523.15 ± 3 490.10, 127 786.35 ± 13 008.86, 237 233.03 ± 47 614.63) and α-SMA (516.83 ± 181.18, 2 885.03 ± 864.92, 11 186.94 ± 2 394.08, 37 182.43 ± 12 390.59) protein levels were also increased significantly ( P < 0.05). Conclusion:Long-term excessive intake of fluorine may cause the production of collagen fibers around the central vein and the portal area of the liver in rats to increase, and then lead to the formation of liver fibrosis.