五苓散对果糖饮食小鼠肝脏炎性损伤的保护作用及其机制研究
首发时间:2016-05-25
摘要:目的:临床和基础研究均证实,摄入过量果糖会引发代谢综合征,并损伤肝脏组织。传统经典方五苓散由猪苓、茯苓、泽泻、肉桂及炒白术组成,具有改善胰岛素抵抗和脂质代谢紊乱、及抗炎等作用,呈现出防治相关代谢性疾病的潜力,但其作用机制仍需探索。因此,本文主要研究五苓散对果糖代谢综合征小鼠肝脏损伤的改善作用,并初步探索其作用机制。方法:雄性ICR小鼠每天饮用30%果糖水,6周后分别给予水、五苓散和别嘌呤醇,持续6周,在此期间每天给予果糖水。测定肝脏组织中甘油三酯、总胆固醇等水平。测定小鼠血清和肝脏组织中IL-1β水平。观察小鼠肝组织病理变化和脂质沉积。检测肝脏JNK/IRS1/Akt信号通路、NF-κB信号通路以及NLRP3炎症小体相关蛋白表达水平。结果:五苓散能显著降低果糖诱导小鼠肝脏甘油三酯和总胆固醇的水平,减少肝组织中的脂质堆积。同时,五苓散减轻肝细胞炎性浸润,显著降低果糖诱导小鼠血清和肝脏IL-1β。五苓散还可调节模型动物肝脏JNK/IRS1/Akt信号通路,抑制NF-κB通路和NLRP3炎症小体的激活。结论:本文研究结果表明,五苓散可改善果糖引起小鼠代谢综合征,改善果糖代谢综合征小鼠肝脏甘油三酯堆积与炎症,其作用机制可能与其调节肝脏胰岛素信号传导、抑制NF-κB通路和NLRP3炎症小体的激活有关。本研究初步揭示了五苓散对果糖代谢综合征小鼠肝脏组织炎症损伤的保护机制,为其临床防治代谢性紊乱疾病肝脏组织损伤提供科学依据。
关键词: 五苓散 高果糖摄入 肝损伤 NLRP3炎症小体 NF-κB
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Study on liver protection of Wuling San and its mechanism in fructose-induced mice
Abstract:Objective:To investigate the protection of Wuling San against liver inflammatory injury and its mechanisms in fructose-induced mice. Methods: ICR mice were fed with 30% fructose in drinking water for 6 weeks. Then mice were orally administrated for next 6 weeks with water, Wuling San, positive drug allopurinol daily, respectively. Results: Wuling San significantly decreased lipid deposition in the liver of fructose-fed mice. It also inhibited hepatic inflammation and reduced serum and hepatic IL-1β levels in fructose-fed mice. Wuling San regulated hepatic insulin signaling, suppressed NF-κB signaling and NLRP3 inflammasome activation in the liver of fructose-fed mice. Conclusion: Wuling San was demonstrated to improve fructose-induced metabolic syndrome in mice. Wuling San also reduced hepatic triglycerides accumulation and inflammation in fructose-induced metabolic syndrome of mice, which may be associated with the regulation of hepatic insulin signaling, suppression of NF-κB signaling and NLRP3 inflammasome activation in this animal model. This study initially reveals liver protection mechanism by which Wuling San allevats inflammation and injury in fructose-induced metabolic syndrome of mice, and may provide scientific basis for the prevention and treatment of metabolic disorders-associated liver injury in the clinical.
Keywords: Wuling San Excess fructose intake Liver protection
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