3-甲基腺嘌呤改善四氯化碳诱导的小鼠肝纤维化及其肠道菌群

目的探讨肠道菌群在3-甲基腺嘌呤(3-MA)改善四氯化碳(CCl_4)介导小鼠肝纤维化过程中的作用。方法 15只小鼠随机分为正常对照组、肝纤维化组和3-MA处理组;用CCl_4构建肝纤维化模型,3-MA处理组第3周开始额外给予3-MA。8周后处死小鼠并取其血液、肝组织及肠道内容物,分析血清ALT、AST和GGT水平、肝组织病理及肠道菌群情况。结果 3-MA处理组血清ALT和AST明显低于肝纤维化组(68.6±4.2) U/L vs (111.0±7.8) U/L,(179.0±12.9) U/L vs (253.2±26.7) U/L,P0.01],且肝组织病变程度减轻。PCoA及NMDS分析将3组小鼠肠道菌群区分。与正常对照组比较,肝纤维化组肠道群落Alpha多样性降低,毛螺菌科丰度显著下降,放线菌门、脱硫弧菌等肠道菌丰度显著升高(P0.05)。与肝纤维化组比较,3-MA处理组肠道群落Alpha多样性增高,毛螺菌科、Blautia菌丰度明显增高,双歧杆菌丰度减低;较正常对照组乳酸杆菌丰度明显增高(P0.05)。结论 3-MA改善了CCl_4介导的小鼠肝纤维化,而肠道菌群可能在此过程中起着积极作用。

3-Methyladenine ameliorates CCl4-mediated liver fibrosis and gut microbiota in mice

Objective To explore the role of gut microbiota in the amelioration of CCl4-mediated hepatic fibrosis in mice by 3-methyladenine(3-MA). Methods Mice were randomly divided into three groups(n=15): mice of liver fibrosis group and 3-MA treatment group received CCl4 to establish liver fibrosis models, and 3-MA treatment group were injected additionally with 3-MA from the third week. The mice were sacrificed after 8 weeks, and samples of blood, liver and fecal samples were collected. We analyzed the serum ALT, AST, GGT levels, histochemical staining of the liver and intestinal flora of each mouse. Results Compared with liver fibrosis group, the serum ALT, AST levels decreased and liver histopathological changes reduced obviously in 3-MA treatment group (68.6 ± 4.2U/L VS 111.0 ±7.8U/L, 179.0 ± 12.9U/L VS 253.2 ± 26.7 U/L, P<0.01). PCoA and NMDS analysis showed that the intestinal flora structural segregated. Alpha diversity estimations revealed lower microbiota diversity in samples from liver fibrosis group. Compared with control group, taxonomic analysis illustrated that the abundance of Lachnospiraceae was declined, while the abundance of Actinobacteria, Desulfovibrionacea and the like were significantly increased(P<0.05). Besides, Alpha diversity estimations in 3-MA treatment group was higher than that in liver fibrosis group and the abundance of Lachnospiraceae and Blautia were obviously enriched, the abundance of Bifidobacteriaceae was decreased(P<0.05). In addition, compared with control group, the abundance of Lactobacillaceae was enriched in3-MA treatment group(P<0.05). Conclusions The gut microbiota may play an active role in the amelioration of CCl4-mediated liver fibrosis in mice by 3-MA.