Department of Pediatrics, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
Department of Pathology, Tianjin Nankai Hospital, Tianjin 300100, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3837-3844. doi: 10.3892/mmr.2017.8284. Epub 2017 Dec 15.
The aim of the present study was to identify the impact of ursodeoxycholic acid (UDCA) on liver function and fibrosis markers in infant rats by establishing a cholestatic‑induced hepatic fibrosis model. α‑naphthylisothiocyanate (ANIT) was administrated by gavage to induce cholestatic hepatic fibrosis in infant rats. UCDA treatment was performed to assess its impact on biochemical indicators of liver function, four serum biomarkers of hepatic fibrosis, hepatic fibrosis indices in liver tissues and the pathology of liver tissues. Colorimetric assays and biochemical assays based on the initial rate method were performed to determine the levels of liver function markers in the serum, whereas the serum biomarkers of hepatic fibrosis were measured via radioimmunoassay. Sections of liver tissue were harvested and stained with hematoxylin‑eosin or picric acid‑Sirius red, and subjected to immunohistochemical staining to analyze liver pathology. All indicators of liver function, except for cholinesterase, were significantly higher in the ANIT model than in the control group (P<0.01). γ‑glutamyl transpeptidase and total bile acids of the UDCA treatment group were significantly lower than the ANIT model (P<0.05); whereas no significant differences were observed in alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and indirect bilirubin between the two groups. Serum laminin protein (LN) and type‑IV collagen (cIV) in the UDCA treatment group were significantly lower than in the ANIT model (P<0.01); whereas no significant differences were observed in hyaluronic acid and type‑III procollagen between the two groups. Liver LN and cIV in the UDCA treatment group were significantly lower than in the ANIT model (P<0.01). The degree of hepatic fibrosis in the UDCA treatment group was significantly lower than in the ANIT model (P<0.01). The results of the present study demonstrated that UDCA is able to reduce LN and cIV in serum and protect liver tissues against hepatic fibrosis.
本研究旨在通过建立胆汁淤积性肝纤维化模型，观察熊去氧胆酸（UDCA）对实验性胆汁淤积性肝纤维化幼鼠肝功能及肝纤维化指标的影响。采用α-萘异硫氰酸酯（ANIT）灌胃诱导幼鼠胆汁淤积性肝纤维化，观察 UDCA 对幼鼠肝功能生化指标、血清肝纤维化四项、肝组织纤维化指标及肝组织病理的影响。采用比色法和初速度法生化法检测血清肝功能标志物水平，放射免疫法检测血清肝纤维化标志物，肝组织病理切片行苏木精-伊红（HE）及苦味酸-天狼猩红染色，免疫组化染色分析肝组织病理。ANIT 模型组除胆碱酯酶外，各肝功能指标均显著高于对照组（P<0.01）；UDCA 治疗组 γ-谷氨酰转肽酶、总胆汁酸显著低于 ANIT 模型组（P<0.05），而丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素、直接胆红素、间接胆红素两组间比较差异无统计学意义。UDCA 治疗组血清层粘连蛋白（LN）、Ⅳ型胶原（cIV）显著低于 ANIT 模型组（P<0.01）；透明质酸、Ⅲ型前胶原两组间比较差异无统计学意义。UDCA 治疗组肝组织 LN、cIV 显著低于 ANIT 模型组（P<0.01）。UDCA 治疗组肝纤维化程度显著低于 ANIT 模型组（P<0.01）。综上所述，UDCA 可降低血清 LN、cIV，对肝组织有保护作用，减轻肝纤维化程度。
