Zhen Yong-Zhan, Li Na-Ren, He Hong-Wei, Zhao Shuang-Shuang, Zhang Guang-Ling, Hao Xiao-Fang, Shao Rong-Guang
Yong-Zhan Zhen, Guang-Ling Zhang, Xiao-Fang Hao, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, Hebei United University, Tangshan 063000, Hebei Province, China.
World J Gastroenterol. 2015 Jun 21;21(23):7155-64. doi: 10.3748/wjg.v21.i23.7155.
To evaluate the protective effect of bicyclol against bile duct ligation (BDL)-induced hepatic fibrosis in rats.
Sprague-Dawley male rats underwent BDL and sham-operated animals were used as healthy controls. The BDL rats were divided into two groups which received sterilized PBS or bicyclol (100 mg/kg per day) orally for two consecutive weeks. Serum, urine and bile were collected for biochemical determinations. Liver tissues were collected for histological analysis and a whole genome oligonucleotide microarray assay. Reverse transcription-polymerase chain reaction and Western blotting were used to verify the expression of liver fibrosis-related genes.
Treatment with bicyclol significantly reduced liver fibrosis and bile duct proliferation after BDL. The levels of alanine aminotransferase (127.7 ± 72.3 vs 230.4 ± 69.6, P < 0.05) and aspartate aminotransferase (696.8 ± 232.6 vs 1032.6 ± 165.8, P < 0.05) were also decreased by treatment with bicyclol in comparison to PBS. The expression changes of 45 fibrogenic genes and several fibrogenesis-related pathways were reversed by bicyclol in the microarray assay. Bicyclol significantly reduced liver mRNA and/or protein expression levels of collagen 1a1, matrix metalloproteinase 2, tumor necrosis factor, tissue inhibitors of metalloproteinases 2, transforming growth factor-β1 and α-smooth muscle actin.
Bicyclol significantly attenuates BDL-induced liver fibrosis by reversing fibrogenic gene expression. These findings suggest that bicyclol might be an effective anti-fibrotic drug for the treatment of cholestatic liver disease.
评估双环醇对胆管结扎（BDL）诱导的大鼠肝纤维化的保护作用。
将Sprague-Dawley雄性大鼠进行胆管结扎，假手术动物作为健康对照。将胆管结扎大鼠分为两组，连续两周分别口服无菌PBS或双环醇（每天100mg/kg）。收集血清、尿液和胆汁进行生化测定。收集肝组织进行组织学分析和全基因组寡核苷酸微阵列分析。采用逆转录-聚合酶链反应和蛋白质印迹法验证肝纤维化相关基因的表达。
双环醇治疗显著减轻了胆管结扎后的肝纤维化和胆管增生。与PBS相比，双环醇治疗还降低了丙氨酸转氨酶水平（127.7±72.3对230.4±69.6，P<0.05）和天冬氨酸转氨酶水平（696.8±232.6对1032.6±165.8，P<0.05）。在微阵列分析中，双环醇逆转了45个纤维化基因的表达变化和几条纤维生成相关途径。双环醇显著降低了肝组织中胶原蛋白1a1、基质金属蛋白酶2、肿瘤坏死因子、金属蛋白酶组织抑制剂2、转化生长因子-β1和α-平滑肌肌动蛋白的mRNA和/或蛋白质表达水平。
双环醇通过逆转纤维化基因表达显著减轻胆管结扎诱导的肝纤维化。这些发现表明双环醇可能是治疗胆汁淤积性肝病的一种有效的抗纤维化药物。
