藏红花素调节Nrf2/HO-1信号通路对肝硬化老年大鼠炎症反应和纤维化的影响

doi:10.3969/j.issn.1006-6233.2025.08.02

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Abstract Objective: To explore the effects of crocin (CR) on inflammation and fibrosis in elderly rats with liver cirrhosis by regulating the nuclear factor E2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Methods: Rat model of liver cirrhosis was established by subcutaneous injection of carbon tetrachloride. The successfully modeled rats were assigned into a model group, L-CR group, M-CR group, H-CR group (intraperitoneal injection of 20, 40, and 80mg/kg CR), and ML385 group (intraperitoneal injection of 80mg/kg CR+intraperitoneal injection of 30mg/kg Nrf2/HO-1 signaling pathway inhibitor ML385), each with 10 rats. In addition, 10 normal rats were recruited as the control group. The control group and model group were intraperitoneally injected with an equal amount of physiological saline, once a day for 4 weeks of continuous intervention. Fully automatic biochemical analyzer was used to detect ALT and AST. The reagent kits were used to measure hyaluronic acid (HA), type III procollagen (PCⅢ), type Ⅳ collagen (Ⅳ-C), and laminin (LN). HE staining was used to observe pathological changes in rat liver tissue. Sirius red staining was used to observe changes in collagen deposition in rat liver tissue. ELISA was used to measure the inflammatory and oxidative stress factors in rat serum. Western blot was used to measure the changes of Nrf2/HO-1 signaling pathway related proteins in rat liver tissue. Results: For the control group, the liver tissue of rats in the model group was disordered, with severe collagen deposition and inflammatory cell infiltration. The ALT, AST, HA, PC Ⅲ, Ⅳ-C, LN, TNF-α, IL-6, IL-1β, and MDA increased (P<0.05), while the SOD, Nrf2, and HO-1 decreased (P<0.05). For the model group, the L-CR group, M-CR group, and H-CR group showed neat arrangement of liver tissue, reduced collagen deposition, and inflammatory cell infiltration. The ALT, AST, HA, PCⅢ, Ⅳ-C, LN, TNF-α, IL-6, IL-1β, and MDA reduced clearly (P<0.05), while SOD, Nrf2, and HO-1 increased clearly (P<0.05). For the H-CR group, the liver tissue arrangement of rats in ML385 group was more disordered, with increased collagen deposition and inflammatory cell infiltration. The ALT, AST, HA, PC Ⅲ, Ⅳ-C, LN, TNF-α, IL-6, IL-1β, and MDA increased clearly (P<0.05), while SOD, Nrf2, and HO-1 decreased clearly (P<0.05). Conclusion: CR may inhibit inflammation and fibrosis in cirrhotic rats by activating Nrf2/HO-1 signaling pathway.

Key words： Crocin Nuclear factor erythroid 2 related factor 2/antioxidant response element 1 Cirrhosis Inflammatory response Fibrosis

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.08.02 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I8/1239

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