目的:在实验性大鼠模型中研究白藜芦醇对α-Amanitin(α-AMA)肝毒性的保护作用。专注于氧化应激,炎症,凋亡,和肝功能。
方法:32只雄性SD大鼠分为4组(每组8只):对照组,白藜芦醇,α-AMA,和白藜芦醇+α-AMA。白藜芦醇组口服20mg/kg白藜芦醇7天。α-AMA组在第8天腹腔注射3mg/kgα-AMA。白藜芦醇+α-AMA组口服20mg/kg白藜芦醇(7天),然后在第8天腹膜内注射3mg/kgα-AMA。α-amanitin给药后48小时收集肝组织和血样,免疫组织化学(NFkB,LC3B),和生化分析(GSH,MDA,CAT,GPx,MPO,NOS,AST,ALT)。
结果:α-AMA显著增加AST和ALT水平,氧化应激标志物(MDA),和炎症标志物(MPO),同时降低抗氧化剂水平(GSH,CAT,GPx)和NOS浓度(所有参数p<0.001)。组织病理学分析显示严重的肝损伤,NFkB和LC3B表达增加。白藜芦醇治疗显著降低AST和ALT水平(P<0.01为两个参数),MDA和MPO水平降低,NOS浓度增加,GSH,CAT,和GPx水平(所有参数p<0.05)。白藜芦醇+α-AMA组中NFkB和LC3B表达降低,并显示组织病理学改善。
结论:白藜芦醇通过减少氧化应激对α-AMA诱导的肝毒性表现出实质性的肝保护作用,炎症,和细胞凋亡,改善肝功能.这些发现表明白藜芦醇可能是治疗由有效肝毒素如α-AMA引起的肝损伤的潜在治疗剂。
OBJECTIVE: The hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function.
METHODS: Thirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT).
RESULTS: α-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements.
CONCLUSIONS: Resveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.