Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis.
Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis.
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DOI：
10.1016/j.alcohol.2008.12.009
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Keshavarzian A
中科院分区：
文献类型：
--
作者：
Forsyth CB;Farhadi A;Jakate SM;Tang Y;Shaikh M;Keshavarzian A
由于只有30%的酗酒者会发展成酒精性肝病（ALD），因此酒精性肝损伤的发展必须涉及除大量饮酒以外的其他因素。动物和人体研究表明，细菌产物如内毒素是第二个关键的辅因子，氧化剂介导的肠道渗漏是内毒素血症的来源之一。益生菌已被用于预防和治疗与肠道衍生的细菌产物相关的疾病和与肠道渗漏相关的病症。事实上，“益生菌”乳酸菌已成功用于治疗酒精诱导的大鼠肝损伤。但是，乳酸杆菌在酒精性肝损伤中的潜在有益作用的作用机制尚不清楚。我们假设益生菌可以通过防止酒精诱导的氧化应激来保护ALD动物模型中的正常屏障功能，从而防止高渗透性和随后的酒精性脂肪性肝炎的发展。雄性Sprague-Dawley大鼠每天两次灌胃酒精（8 gm/kg），持续10周。此外，酒精中毒大鼠也进行了治疗，每天一次管饲的2.5 × 107活乳杆菌GG（LGG）或车辆。肠通透性（基线和10周）使用糖丸和尿糖GC分析确定。分析肠和肝组织的氧化应激和炎症标志物。此外，还对肝脏进行了酒精性脂肪性肝炎（ASH）和总脂肪（脂肪变性）严重程度的组织学评估。酒精-LGG喂养大鼠的ASH严重程度显著低于酒精-溶剂喂养大鼠（p≤ 0.05）。LGG还改善了酒精诱导的肠道渗漏，并显着减弱了酒精诱导的氧化应激和肠道和肝脏炎症。LGG益生菌灌胃显著改善大鼠酒精性脂肪性肝炎。这种改善与肠道和肝脏氧化应激和炎症标志物的减少以及肠道屏障功能的保护有关。我们的研究为测试益生菌治疗和/或预防人类酒精性肝病提供了科学依据。
Since only 30% of alcoholics develop alcoholic liver disease (ALD), a factor other than heavy alcohol consumption must be involved in development of alcohol-induced liver injury. Animal and human studies suggest that bacterial products such as endotoxin are the second key co-factor and oxidant-mediated gut leakiness is one of the sources of endotoxemia. Probiotics have been used to prevent and treat diseases associated with gut-derived bacterial products and disorders associated with gut leakiness. Indeed, “probiotic” Lactobacillus has been successfully used to treat alcohol-induced liver injury in rats. But, the mechanism of action of the potential beneficial effects of Lactobacillus in alcohol liver injury is not known. We hypothesized that probiotics could preserve normal barrier function in an animal model of ALD by preventing alcohol-induced oxidative stress and thus prevent development of hyperpermeability and subsequent alcoholic steatohepatitis. Male Sprague-Dawley rats were gavaged with alcohol twice daily (8gm/kg) for 10 weeks. In addition, alcoholic rats were also treated with once daily gavage of either 2.5 107 live Lactobacillus GG (LGG) or vehicle. Intestinal permeability (baseline and 10wk) was determined using a sugar bolus and GC analysis of urinary sugars. Intestinal and liver tissues were analyzed for markers of oxidative stress and inflammation. In addition livers were assessed histologically for severity of alcoholic steatohepatitis (ASH) and total fat (steatosis). Alcohol-LGG fed rats had significantly (p≤ .05) less severe ASH than alcohol-vehicle fed rats. LGG also improved alcohol-induced gut leakiness and significantly blunted alcohol-induced oxidative stress and inflammation in both intestine and the liver. LGG probiotic gavage significantly ameliorated alcoholic steatohepatitis in rats. This improvement was associated with reduced markers of intestinal and liver oxidative stress and inflammation and preserved gut barrier function. Our study provides a scientific rationale to test probiotics for treatment and/or prevention of alcoholic liver disease in man.
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影响因子：
25.7
作者：
Chiva, M;Soriano, G;Balanzó, J
通讯作者：
Balanzó, J
影响因子：
4.2
作者：
Eutamene, Helene;Lamine, Florence;Bueno, Lionel
通讯作者：
Bueno, Lionel
影响因子：
5.5
作者：
Banan, A;Zhang, LJ;Keshavarzian, A
通讯作者：
Keshavarzian, A
影响因子：
24.5
作者：
García-Lafuente, A;Antolín, M;Malagelada, JR
通讯作者：
Malagelada, JR
DOI：
10.1097/01.alc.0000189280.19073.28
发表时间：
2005-11-01
影响因子：
3.2
作者：
Bode, C;Bode, JC
通讯作者：
Bode, JC