Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Inflammation. 2022 Apr;45(2):812-823. doi: 10.1007/s10753-021-01586-w. Epub 2022 Jan 26.
Hepatic fibrosis (HF) is the typical response to chronic liver disease and is characterized by deposition of abundant extracellular matrix. The aim of the present study was to investigate the protective effect of resveratrol (RSV) in a CCl-induced rat model of HF. We demonstrate that the administration of RSV effectively improves liver function and ameliorates liver fibrosis by reducing collagen deposition and reversing the expression of COL1A1 and PPAR-γ. Treatment efficacy of RSV could be attributed to reversed epithelial-mesenchymal transition progress with upregulated expression of E-cadherin and downregulated N-cadherin, vimentin, and α-SMA. Moreover, RSV significantly decreased the levels of endoplasmic reticulum stress (ERS)-related proteins CHOP; Bip; cleaved caspase-3, caspase-7, and caspase-12; Bax; and Bak while promotes the expression of anti-apoptosis protein Bcl2. The important role of ERS in HF was confirmed by using 4-PBA, an ERS inhibitor, which markedly ameliorated CCl-induced HF. Further, mechanistic studies demonstrated that RSV significantly decreased CCl-induced transforming growth factor-β synthesis and inflammatory factor (tumor necrosis factor-α and interleukin-6) expression and reduced the inflammation of hepatic stellate cells by inhibiting the NF-κB pathway in vivo and in vitro. In conclusion, the results suggested that RSV ameliorated HF in associated with decreased ERS-induced apoptosis and inflammation in rats.
肝纤维化（HF）是慢性肝病的典型反应，其特征是大量细胞外基质的沉积。本研究旨在探讨白藜芦醇（RSV）在 CCl 诱导的 HF 大鼠模型中的保护作用。我们证明 RSV 的给药可通过减少胶原蛋白沉积和逆转 COL1A1 和 PPAR-γ 的表达，有效改善肝功能并改善肝纤维化。RSV 的治疗效果可归因于上皮-间充质转化过程的逆转，表现为 E-钙黏蛋白表达上调，N-钙黏蛋白、波形蛋白和α-SMA 表达下调。此外，RSV 还显著降低了内质网应激（ERS）相关蛋白 CHOP、Bip、裂解的 caspase-3、caspase-7 和 caspase-12、Bax 和 Bak 的水平，同时促进了抗凋亡蛋白 Bcl2 的表达。使用 ERS 抑制剂 4-PBA 证实了 ERS 在 HF 中的重要作用，其可显著改善 CCl 诱导的 HF。此外，机制研究表明 RSV 可通过抑制体内和体外的 NF-κB 通路，显著降低 CCl 诱导的转化生长因子-β合成和炎症因子（肿瘤坏死因子-α和白细胞介素-6）表达，减轻肝星状细胞的炎症。总之，这些结果表明 RSV 通过减少 ERS 诱导的细胞凋亡和炎症改善了 HF。
