Schneider Ana Claudia Reis, Machado Alice Beatriz Mombach Pinheiro, de Assis Adriano Martimbianco, Hermes Djuli Milene, Schaefer Pedro Guilherme, Guizzo Ranieli, Fracasso Laísa Beduschi, de-Paris Fernanda, Meurer Fábio, Barth Afonso Luis, da Silveira Themis Reverbel
1 Programa de Pós-Graduação: Ciências em Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul , Porto Alegre, Brazil .
Zebrafish. 2014 Aug;11(4):371-8. doi: 10.1089/zeb.2013.0968. Epub 2014 Jul 2.
Zebrafish is a powerful tool in pharmacological research and useful to identify new therapies. Probiotics can offer therapeutic options in alcoholic liver disease. This study was done in two independent experiments: first, we confirmed the intestinal colonization of probiotic Lactobacillus rhamnosus GG (LGG) after ethanol exposure. Second, four groups were performed: control (C), probiotic (P), ethanol (E), and probiotic+ethanol (P+E). Liver histology, hepatocytes morphometry, hepatic and serum lipid quantifications were conducted in second experiment. During 4 weeks, P and P+E groups were fed with LGG supplemented feed; E and C unsupplemented. E and P+E groups received 0.5% of ethanol added into tank water. Zebrafish exposed to ethanol (E group) presented intense liver steatosis after 28 days in contrast to the almost normalized liver histology of P+E group at the same period. Liver morphometry showed a significant enlargement of hepatocytes of E group after 4 weeks (p<0.0001). Serum triglycerides decreased in P+E group compared with C, P (p<0.001), and E (p=0.004), after 14 and 28 days similarly. Serum cholesterol was also decreased by LGG; P group decreased compared with C and E after 14 days (p=0.002 and p=0.007, respectively) and P+E group decreased significantly compared with E and C groups (p<0.0001) after 28 days. Hepatic triglycerides were reduced in P+E group after 28 days compared to E (p=0.006). The persistence of LGG in zebrafish intestines was demonstrated. LGG decreased serum levels of triglycerides and cholesterol and improved hepatic steatosis.
斑马鱼是药理学研究中的有力工具,有助于确定新的治疗方法。益生菌可为酒精性肝病提供治疗选择。本研究通过两个独立实验完成:首先,我们证实了乙醇暴露后益生菌鼠李糖乳杆菌GG(LGG)在肠道的定植。其次,分为四组:对照组(C)、益生菌组(P)、乙醇组(E)和益生菌+乙醇组(P+E)。在第二个实验中进行了肝脏组织学、肝细胞形态计量学、肝脏和血清脂质定量分析。在4周内,P组和P+E组喂食添加LGG的饲料;E组和C组不添加。E组和P+E组在养殖水中添加0.5%的乙醇。与同期P+E组肝脏组织学几乎正常化相比,暴露于乙醇的斑马鱼(E组)在28天后出现严重肝脂肪变性。肝脏形态计量学显示,4周后E组肝细胞显著肿大(p<0.0001)。同样,在14天和28天后,P+E组血清甘油三酯与C组、P组(p<0.001)和E组(p=0.004)相比均下降。LGG也降低了血清胆固醇;14天后P组与C组和E组相比降低(分别为p=0.002和p=0.007),28天后P+E组与E组和C组相比显著降低(p<0.0001)。28天后,P+E组肝脏甘油三酯与E组相比降低(p=0.006)。证实了LGG在斑马鱼肠道中的持久性。LGG降低了血清甘油三酯和胆固醇水平,并改善了肝脂肪变性。