Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil.
Department of Biosciences, Instituto Saúde Sociedade, Universidade Federal de São Paulo, Santos 11015-020, Brazil.
Molecules. 2022 Jan 20;27(3):654. doi: 10.3390/molecules27030654.
During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.
在肝纤维化过程中,再生和伤口愈合之间存在失衡。目前的治疗方法是去除致病因子;因此,研究新的有效治疗方法很重要。研究已经强调了硫酸软骨素(CS)在不同细胞中的作用;因此,我们的目的是分析其在胆管结扎(BDL)实验模型中的作用。成年 Wistar 大鼠接受 BDL 并通过腹膜内注射 CS 治疗 7、14、21 或 28 天。我们对 Picrosirius 染色的肝组织切片进行组织形态计量学分析。根据 caspase-3 和组织蛋白酶 B 的活性以及使用 TUNEL 测定法分析细胞死亡。使用 PCNA 免疫组织化学评估再生。BDL 导致胶原含量增加,相应的肝实质减少。CS 治疗在 21 天和 28 天后减少总胶原并增加实质含量。该治疗还促进了肝胶原 III/I 比值的变化。此外,观察到 CS 治疗在 14 天后降低了 caspase-3 活性和 TUNEL 阳性细胞的百分比,而仅在 28 天后降低了组织蛋白酶 B 的活性。CS 治疗后 14、21 和 28 天,再生增加。总之,我们的研究表明 CS 在 BDL 诱导的纤维化中具有有希望的肝保护作用。