Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6-p47(phox) Oxidative-Stress Axis.
Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6-p47(phox) Oxidative-Stress Axis.
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DOI：
10.3390/cells11081305
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发表时间：
2022-04-12
期刊：
影响因子：
6
通讯作者：
Cui, Di
中科院分区：
文献类型：
--
作者：
Cui, Wei;Li, Xiang;Xue, Weiyue;Wei, Huiting;Zhou, Gang;Qiu, Ye;Cui, Di
关键词：
(1)背景资料：探讨运动对酒精性肝病（ALD）形成和恢复的影响，以及IL-6-p47 phox氧化应激轴是否参与了这一过程。(2)研究方法：首先，将23只6周龄雄性C57 BL/6 J小鼠随机分为Con组、ALD组、ALD + NOXI组、ALD + Ex组和ALD + Ex + NOXI组。采用Liber-DeCarli酒精性液体饲料喂养6周建立ALD小鼠模型，Con组给予TP 4030 C对照饲料。其余各组均给予TP 4030 B酒精性饲料喂养，并在ALD模型建立后开始运动干预，持续6周，在每个运动训练日腹腔注射或不注射NOX抑制剂夹竹桃素。将28只小鼠随机分为Sed组、Eth组、Eth + Ex组和Eth + Ex + NOXI组。Sed组给予TP 4030 C对照饲料。其余各组均喂以TP 4030 B酒精饮食，并在每个运动训练日同步开始运动干预，同时联合或不联合腹腔注射夹竹桃苷，持续5周。在每个单独的实验完成后，检查血液和组织样品的生理评估和生化分析。(3)结果如下：ALD组血清TG水平和肝组织IL-6蛋白含量较Con组显著升高（p < 0.05），ALD + NOXI组肌肉组织p47 phox表达较ALD组显著升高（p < 0.05），ALD + Ex组血清TG水平较ALD组显著降低（p < 0.05）。ALD + Ex + NOXI组血清TG、AST/ALT比值、肝脏和肌肉中IL-6含量显著降低（p < 0.05），肌肉中MDA含量显著升高（p < 0.01）。与ALD + NOXI组相比，ALD + Ex + NOXI组AST/ALT比值、血清TG、肝脏SOD、肝脏和肌肉中p47 phox均显著降低（p < 0.01）。与ALD + Ex组相比，ALD + Ex + NOXI组肝指数和血清HDL-C水平降低（p < 0.05）。运动干预后肝细胞脂肪变性和炎症浸润程度明显减轻。Eth组附睾相对脂肪含量、HDL-C水平、AST/ALT比值显著低于Sed组，肝脏TG和gp 91 phox显著高于Sed组（p < 0.05，p < 0.01）。与Eth组相比，Eth + Ex组AST/ALT比值、肝脏MDA含量、肝脏NOX 4和p47 phox蛋白表达显著升高（p < 0.05，p < 0.01），体重显著降低（p < 0.05，p < 0.01），肝脏TG含量和肌肉MDA含量也显著升高。在th + Ex + NOXI组中，肝中gp 91 phox表达和体重显著降低（p < 0.05，p < 0.01）。与Eth + Ex组相比，Eth + Ex + NOXI组肌肉组织中AST/ALT比值和MDA含量升高，gp 91 phox和p47 phox蛋白表达降低（p < 0.01）。(4)结论：在ALD的恢复期进行6周的运动干预可通过IL-6-p47 phox氧化应激轴改善肝细胞损伤和血脂异常，联合应用NOX抑制剂可优化这一点。然而，运动时饮酒会加重血脂异常和氧化应激，肝细胞IL-6-p47 phox下调。
(1) Background: To explore the effect of exercise on the formation and recovery of alcoholic liver disease (ALD) and whether the IL-6–p47phox oxidative–stress axis is involved in that process. (2) Methods: Firstly, 23 six-week-old male C57BL/6J mice were randomly divided into the Con group, ALD group, ALD + NOXI group, ALD + Ex group, and ALD + Ex + NOXI group. The Liber–DeCarli alcoholic liquid diet was used for 6 weeks to establish the ALD mice model, and the Con group was given the TP4030C control diet. The remaining groups were fed with the TP4030B alcoholic diet, and exercise intervention was started after the ALD model establishment and lasted for another 6 weeks, with or without administration of the NOX inhibitor apocynin by intraperitoneal injection on every exercise training day. Secondly, 28 mice were randomly divided into the Sed group, Eth group, Eth + Ex group and Eth + Ex + NOXI group. The Sed group was given the TP4030C control diet. The remaining groups were fed with the TP4030B alcoholic diet and exercise intervention was started synchronously combined with or without administration of intraperitoneal apocynin injections on every exercise training day for 5 weeks. After each individual experiment was accomplished, physiological assessment and biochemical analysis of blood and tissue samples were examined. (3) Results: The levels of TG in serum and IL-6 protein content in liver tissue in the ALD group were significantly increased compared to the Con group (p < 0.05); compared with ALD, p47phox expression in muscle was increased significantly in the ALD + NOXI group (p < 0.05), and TG in serum decreased in the ALD + Ex group (p < 0.05). TG in serum, AST/ALT ratio, and IL-6 content in both liver and muscle decreased (p < 0.05) in the ALD + Ex + NOXI group with MDA in muscle significantly increased (p < 0.01). The AST/ALT ratio, TG in serum, SOD in liver, and p47phox in both liver and muscle in the ALD + Ex + NOXI group were significantly decreased compared with the ALD + NOXI group (p < 0.01). Compared with the ALD + Ex group, the liver index and HDL-C levels in serum were decreased (p < 0.05) in the ALD + Ex + NOXI group. The degree of hepatocyte steatosis and inflammatory infiltration were ameliorated after exercise intervention. In the Eth group, the relative epididymal fat content, HDL-C level, and AST/ALT ratio were significantly decreased, and TG and gp91phox in liver were significantly higher than in the Sed group (p < 0.05, p < 0.01). Compared with the Eth group, the AST/ALT ratio, MDA in the liver, and NOX4 and p47phox protein expression in the liver were significantly increased, and body weight decreased significantly in the Eth + Ex group (p < 0.05, p < 0.01), as did TG in the liver and MDA in muscle. In the th + Ex + NOXI group, gp91phox expression in the liver and body weight were significantly decreased (p < 0.05, p < 0.01). In the Eth + Ex + NOXI group, the ratio of AST/ALT and MDA in muscle were increased when compared with the Eth + Ex group, and the protein expression of gp91phox and p47phox were much lower (p < 0.01). (4) Conclusions: 6 weeks of exercise intervention during the recovery phase of ALD ameliorates hepatocyte damage and dyslipidemia through the IL-6–p47phox oxidative–stress axis, and applying a NOX inhibitor in combination could optimize this. However, drinking alcohol during exercise exacerbates dyslipidemia and oxidative stress, with hepatocyte IL-6–p47phox downregulated.
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