Buko Vyacheslav U, Lukivskaya Oxana Y, Naruta Elena E, Belonovskaya Elena B, Tauschel Horst-Dietmar
Division of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK-50, Grodno 230030, Belarus ; School of Medical Sciences, Krakowska Str. 9, 15-875 Bialystok, Poland.
Division of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK-50, Grodno 230030, Belarus.
J Clin Exp Hepatol. 2014 Dec;4(4):293-301. doi: 10.1016/j.jceh.2014.02.001. Epub 2014 Feb 21.
BACKGROUND/OBJECTIVES: Effects of norursodeoxycholic acid (norUDCA) and ursodeoxycholic acid (UDCA) on liver fibrosis progression and liver fibrosis reversal in thioacetamide (TAA)-treated rats were studied.
Advanced liver fibrosis was induced by TAA treatment (200 mg/kg, i.p.) for 12 weeks. In the second experiment resolution of liver fibrosis was assessed after 8 weeks of TAA withdrawal. During 8 last weeks of each trial, fibrotic rats were daily administered with UDCA (80 mg/kg) and norUDCA (equimolar to 80 mg/kg of UDCA) by oral gavage. Liver fibrosis was assessed by Sirius red staining, liver hydroxyproline and serum fibrosis markers determination.
The TAA treatment resulted in advanced fibrosis and increase in liver hydroxyproline content and serum fibrosis markers. These signs of fibrosis were less pronounced in rats after TAA withdrawal. Treatment with of norUDCA significantly decreased the total and relative liver hydroxyproline contents in rats with fibrosis reversal, whereas UDCA did not change these parameters. Both compounds decreased serum TGFβ and type IV collagen contents, whereas other serum markers did not differ from the placebo group. In the fibrosis progression model the square of connective tissue was decreased by norUDCA. Serum type IV collagen and procollagen III-NT contents in these experiments were lowered by both UDCA and norUDCA, whereas rest of serum fibrosis markers were diminished only by norUDCA.
Both norUDCA and UDCA showed therapeutic and prophylactic antifibrotic effect in rats with TAA-induced liver fibrosis. For most of tested parameters norUDCA was more effective than UDCA, especially in the experiment with liver fibrosis regression.
背景/目的：研究了去氧熊去氧胆酸（norUDCA）和熊去氧胆酸（UDCA）对硫代乙酰胺（TAA）处理的大鼠肝纤维化进展及肝纤维化逆转的影响。
通过腹腔注射TAA（200mg/kg）处理12周诱导进展性肝纤维化。在第二项实验中，TAA撤药8周后评估肝纤维化的消退情况。在每项试验的最后8周期间，通过口服灌胃每日给予纤维化大鼠UDCA（80mg/kg）和norUDCA（与80mg/kg UDCA等摩尔）。通过天狼星红染色、肝脏羟脯氨酸和血清纤维化标志物测定评估肝纤维化。
TAA处理导致进展性纤维化，肝脏羟脯氨酸含量和血清纤维化标志物增加。TAA撤药后大鼠的这些纤维化体征不那么明显。norUDCA治疗显著降低了肝纤维化逆转大鼠的肝脏总羟脯氨酸含量和相对羟脯氨酸含量，而UDCA未改变这些参数。两种化合物均降低了血清TGFβ和IV型胶原含量，而其他血清标志物与安慰剂组无差异。在肝纤维化进展模型中，norUDCA使结缔组织面积减小。在这些实验中，UDCA和norUDCA均降低了血清IV型胶原和前胶原III-NT含量，而其余血清纤维化标志物仅被norUDCA降低。
norUDCA和UDCA在TAA诱导的肝纤维化大鼠中均显示出治疗和预防性抗纤维化作用。对于大多数测试参数，norUDCA比UDCA更有效，尤其是在肝纤维化消退实验中。
