天然产物通过抑制PI3K信号通路抗肝纤维化的研究进展

肝纤维化是慢性肝损伤的一种内在反应,其特征是细胞外基质(extracellular matrix, ECM)的合成、降解和沉积失衡,会导致肝细胞受损和肝脏正常结构被破坏。而肝星状细胞(hepatic stellate cells, HSCs)的异常激活被认为是驱动肝纤维化的关键因素。在肝损伤的过程中,HSCs能够活化并向肌成纤维细胞转化进而产生过量的ECM。炎症和氧化应激在HSCs的激活中发挥重要作用,而HSCs凋亡则有利于肝纤维化的消退。抑制磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase, PI3K)信号通路可降低炎症反应、氧化应激,诱导HSCs凋亡,从而改善肝纤维化。来源于植物的天然产物,包括黄酮类和萜类可以抑制PI3K信号通路,对肝纤维化的发生发展起到抑制作用。该文旨在综述PI3K信号通路在肝纤维化中的作用,总结近年来黄酮类化合物和萜类化合物通过抑制PI3K信号通路抗肝纤维化作用的证据,为进一步开发能有效防治肝纤维化的药物提供参考。     

Effect of Sea Cucumber Enzymolysis Fermentation Liquid on immunosuppressed mice based on metabonomics北大核心CSCD

Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4+and CD8+T lymphocyte subsets and the pro-portion of CD4 /CD8 T lymphocyte subsets in peripheral blood were detected by flow cytometry. The con¬tents of IL-2 ( interleukin-2 ), IgG ( immunoglobulin G) and IgM (immunoglobulin G) in serum were detected by ELISA. The changes of endogenous metabolites in mouse serum were analyzed by UPLC-Q/TOF-MS metabolomics, and the related metabolic pathways were explored. Results SCEFL could improve the pathological changes of immunosuppressed mice, in¬crease the proportion of CD4 T cells and the proportion of CD4+/CD8+T lymphocyte subsets,and increase the contents of IL-2, IgG and IgM in serum. The immune function of mice was regulated mainly through six related metabolic pathways, including glyc-erophospholipid metabolism, sphingolipid metabolism, linoleic acid metabolism, a-linoleic acid metabolism, glycophosphatidylinositol-anchored biosynthesis and arachidonic acid metabolism. Conclusion SCEFL may ameliorate the immunosuppression of mice by regulating endogenous metabolic disorder. © 2023 Publication Centre of Anhui Medical University. All rights reserved.