Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B.
Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B.
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槲皮素通过磷酸肌醇3-激酶和核因子-κ B 对小鼠剧烈运动后内质网应激和炎症的保肝作用
DOI：
10.1155/2016/8696587
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发表时间：
2016
影响因子：
--
通讯作者：
Yao P
中科院分区：
文献类型：
--
作者：
Tang Y;Li J;Gao C;Xu Y;Li Y;Yu X;Wang J;Liu L;Yao P
剧烈运动引起肝损伤的机制及其潜在的治疗方法尚不清楚。我们探讨了槲皮素（一种天然黄酮类化合物）在剧烈运动引起的内质网应激（ERS）和炎症中的保肝作用和机制。剧烈运动（28 m/min，5°坡度，持续90 min）导致BALB/C小鼠中转氨酶的渗漏。槲皮素（100 mg/kg·bw）可减轻肝脏超微结构的畸形和氧化应激水平。槲皮素可降低剧烈运动和毒胡萝卜素（Tg-）诱导的ERS（葡萄糖调节蛋白78，GRP 78）和炎性细胞因子（IL-6和TNF-α）水平。此外，槲皮素导致磷脂酰肌醇3-激酶（PI 3 K）的诱导，Ca 2+的恢复，以及Jun N-末端激酶（JNK），活化转录因子6（ATF 6），尤其是NF-κB（p65和p50核转位）的活性的阻断。一种PI 3 K抑制剂消除了槲皮素对ERS和小鼠肝细胞炎症的保护作用。SP 600125（JNK抑制剂）、AEBSF（ATF 6抑制剂），尤其是PDTC（NF-κB抑制剂）可增强槲皮素诱导的抗Tg刺激的保护作用。总的来说，剧烈运动引起的ERS和炎症被槲皮素减弱。PI 3 K/Akt的激活和JNK、ATF 6的抑制，尤其是NF-κB的抑制参与了保护作用。我们的研究结果强调了一种新的预防策略，用于治疗ERS和炎症介导的肝损伤引起的剧烈运动使用天然植物化学物质。
The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.