Peng Wei, Zhang Shiwen, Zhou Wei, Zhao Xinchen, Wang Kexue, Yue Chengxu, Wei Xinyu, Pang Siyan, Dong Wei, Chen Sulian, Chen Changjie, Yang Qingling, Wang Wenrui
Anhui Province Key Laboratory of Translational Cancer Research, Department of Biotechnology, Bengbu Medical College, Anhui, China.
Department of Biochemistry, School of Laboratory Medicine, Bengbu Medical College, Anhui, China.
Front Bioeng Biotechnol. 2022 May 27;10:873971. doi: 10.3389/fbioe.2022.873971. eCollection 2022.
A core feature of liver fibrosis is the activation of hepatic stellate cells (HSCs), which are transformed into myofibroblasts and lead to the accumulation of extracellular matrix (ECM) proteins. In this study, we combined cellular efficacy with antifibrosis performance to evaluate the outcome of sorafenib (SRF) loaded layered double hydroxide (LDH) nanocomposite (LDH-SRF) on HSCs. The cellular uptake test has revealed that sorafenib encapsulated LDH nanoparticles were efficiently internalized by the HSC-T6 cells, synergistically inducing apoptosis of hepatic stellate cells. Moreover, the apoptosis rate and the migration inhibition rate induced by LDHs-SRF were 2.5 and 1.7 times that of SRF. Western Blot showed that the TGF-β1/Smad/EMT and AKT signaling pathway was significantly inhibited in HSC-T6 cells treated with LDHs-SRF. For the experiment, LDHs-SRF were administered to rat models of CCl-induced liver fibrosis. H&E, masson and sirius red staining showed that LDHs-SRF could significantly reduce inflammatory infiltrate and collagen fiber deposition and immunohistochemical results found that LDHs-SRF treatment significantly inhibited the protein expressions of α-SMA in the liver, these results suggesting that LDHs-SRF exhibited better anti-fibrotic effect than SRF alone and significantly inhibited the proliferation and activation of rat hepatic stellate cells and collagen fiber synthesis.
肝纤维化的一个核心特征是肝星状细胞（HSCs）的激活，这些细胞会转化为肌成纤维细胞并导致细胞外基质（ECM）蛋白的积累。在本研究中，我们将细胞效能与抗纤维化性能相结合，以评估负载索拉非尼（SRF）的层状双氢氧化物（LDH）纳米复合材料（LDH-SRF）对肝星状细胞的作用效果。细胞摄取试验表明，包裹索拉非尼的LDH纳米颗粒被HSC-T6细胞有效内化，协同诱导肝星状细胞凋亡。此外，LDHs-SRF诱导的凋亡率和迁移抑制率分别是SRF的2.5倍和1.7倍。蛋白质印迹法显示，用LDHs-SRF处理的HSC-T6细胞中，TGF-β1/Smad/EMT和AKT信号通路受到显著抑制。在实验中，将LDHs-SRF施用于CCl诱导的肝纤维化大鼠模型。苏木精-伊红染色、Masson染色和天狼星红染色显示，LDHs-SRF可显著减少炎症浸润和胶原纤维沉积，免疫组化结果发现，LDHs-SRF治疗可显著抑制肝脏中α-SMA的蛋白表达，这些结果表明，LDHs-SRF比单独使用SRF表现出更好的抗纤维化作用，可显著抑制大鼠肝星状细胞的增殖和激活以及胶原纤维合成。
