Ionică Floriana Elvira, Mogoantă LaurenŢiu, Nicola Gabriela Camelia, ChiriŢă Cornel, Negreş Simona, Bejenaru Cornelia, Turculeanu Adriana, Badea Oana, Popescu Nicoleta Laura, Bejenaru Ludovic Everard
Department of Vegetal & Animal Biology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania;
Rom J Morphol Embryol. 2016;57(4):1261-1272.
Liver fibrosis is the increasingly accumulation of extracellular matrix (ECM), caused by chronic liver injuries, and represents a difficult clinical challenge in the entire world. Currently, the advanced knowledge of the cellular and molecular mechanisms of liver fibrosis showed that collagen-producing cells, like activated hepatic stellate cells (HSCs), portal fibroblasts and myofibroblasts are activated by fibrogenic cytokines, such as angiotensin II, transforming growth factor-beta 1 (TGF-β1), and leptin. Because of these, we tested telmisartan, an angiotensin II (AT1) receptor blocker and a peroxisome proliferator-activated receptor-γ (PPARγ) partial agonist, for investigate its antifibrotic action, on experimental model of carbon tetrachloride-induced liver fibrosis.
In this research, we used two groups of Wistar rats, which received intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) 40% dissolved in olive oil, twice weekly for four consecutive weeks (initial dose of 5 mL÷kg, and other doses 3 mL÷kg). After one week, one group was received by gavage telmisartan (TS) dissolved in saline 0.9%, daily in dose of 8 mg÷kg, for 28 days. One group of Wistar rats was used for control. The antifibrotic action of telmisartan was investigated on the pathological changes of the liver and immunohistochemical analysis for hepatic stellate (Ito) cells (HSCs) reaction using anti-alpha-smooth muscle actin (anti α-SMA) antibody and macrophages cells (Kupffer cells) reaction using anti-CD68 antibody.
In group treated with telmisartan, hepatic fibrogenesis process was significantly reduced, in comparison with CCl4 group.
肝纤维化是由慢性肝损伤导致的细胞外基质（ECM）逐渐积累，是全球面临的一项严峻临床挑战。目前，关于肝纤维化细胞和分子机制的深入研究表明，产生胶原蛋白的细胞，如活化的肝星状细胞（HSCs）、门静脉成纤维细胞和平滑肌成纤维细胞，会被促纤维化细胞因子激活，如血管紧张素II、转化生长因子-β1（TGF-β1）和瘦素。基于此，我们测试了替米沙坦，一种血管紧张素II（AT1）受体阻滞剂和过氧化物酶体增殖物激活受体-γ（PPARγ）部分激动剂，以研究其在四氯化碳诱导的肝纤维化实验模型中的抗纤维化作用。
在本研究中，我们使用了两组Wistar大鼠，它们每周两次腹腔内（i.p.）注射溶解于橄榄油中的40%四氯化碳（CCl4），连续四周（初始剂量为5 mL÷kg，其他剂量为3 mL÷kg）。一周后，一组通过灌胃给予溶解于0.9%生理盐水中的替米沙坦（TS），每日剂量为8 mg÷kg，持续28天。一组Wistar大鼠用作对照。通过肝脏病理变化以及使用抗α平滑肌肌动蛋白（抗α-SMA）抗体对肝星状（Ito）细胞（HSCs）反应和使用抗CD68抗体对巨噬细胞（库普弗细胞）反应进行免疫组织化学分析，研究替米沙坦的抗纤维化作用。
与CCl4组相比，替米沙坦治疗组的肝纤维化形成过程显著减少。
