用绞股蓝缓解大鼠非酒精性脂肪肝病过程中肠道微生物群的结构调节。

BACKGROUND: The current work aimed to assess whether Gynostemma pentaphyllum (GP), a Chinese herbal medicine, structurally modifies the gut microbiota in rats during non-alcoholic fatty liver disease (NAFLD) treatment. METHODS: High-fat diet (HFD)-induced NAFLD rats were orally administered water decoction of GP or equal amounts of distilled water per day for 4 weeks. Liver tissues were examined by histopathological observation, while intestinal tissues were examined by both histopathological and ultrastructural observations. The levels of fasting blood glucose (FBG), fasting serum insulin (FINS), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) were measured by enzymatic method. The levels of toll-like receptor 4 (TLR-4), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and interleukin-6 (IL-6) in both serum and hepatic tissues were measured by RT-qPCR. The protein expression level of TLR-4 in hepatic tissues was detected by western blot. The gut microbiota was assessed by 16S rRNA-based microbiota analysis. RESULTS: GP maintained intestinal integrity and reversed gut dysbiosis in high-fat diet (HFD)-induced NAFLD rats. This also reduced the ratio of Firmicutes to Bacteroidetes, enriching the abundance of beneficial bacteria (Lactococcus spp.) and inhibiting the abundance of pathogenic bacteria (Ruminococcus spp.) in the gut. The levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and the expression of TLR4 were downregulated (P < 0.05), while the insulin resistance index, HOMA-IR showed improvement by GP treatment (P < 0.05). Liver function indicators (ALT and AST) were remarkably decreased (P < 0.01). Besides, GP treatment reduced TG and LDL-C levels (P < 0.05), and increased HDL-C level (P < 0.05) compared with NAFLD group. CONCLUSION: The structural alterations of gut microbiota induced by GP are associated with NAFLD alleviation.

背景：本研究旨在评估绞股蓝（GP）这种中草药是否能在非酒精性脂肪性肝病（NAFLD）治疗过程中改变大鼠肠道微生物群的结构。

方法：采用高脂饮食（HFD）诱导 NAFLD 大鼠，每天分别给予 GP 水提液或等体积蒸馏水灌胃 4 周。通过组织病理学观察检测肝组织，通过组织病理学和超微结构观察检测肠组织。采用酶法检测空腹血糖（FBG）、空腹血清胰岛素（FINS）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、丙氨酸转氨酶（ALT）和天门冬氨酸转氨酶（AST）水平。采用 RT-qPCR 检测血清和肝组织中 toll 样受体 4（TLR-4）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的水平。采用 Western blot 检测肝组织中 TLR-4 的蛋白表达水平。采用 16S rRNA 微生物分析评估肠道微生物群。

结果：GP 维持了肠道的完整性，并逆转了高脂肪饮食（HFD）诱导的 NAFLD 大鼠的肠道菌群失调。这也降低了厚壁菌门与拟杆菌门的比例，增加了有益菌（乳球菌属）的丰度，抑制了肠道致病菌（真杆菌属）的丰度。促炎细胞因子（TNF-α、IL-1β 和 IL-6）水平和 TLR4 表达下调（P<0.05），而 GP 治疗后胰岛素抵抗指数 HOMA-IR 得到改善（P<0.05）。肝功能指标（ALT 和 AST）显著降低（P<0.01）。此外，GP 治疗组 TG 和 LDL-C 水平降低（P<0.05），HDL-C 水平升高（P<0.05），与 NAFLD 组相比。

结论：GP 引起的肠道微生物群结构改变与 NAFLD 的缓解有关。