小檗碱通过调节肠道菌群改善高脂饮食诱导的非酒精性脂肪性肝病大鼠肝组织炎症实验研究*

doi:10.3969/j.issn.1672-5069.2023.01.007

摘要/Abstract

摘要： 目的探讨应用小檗碱(BBR)处理对高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)大鼠肝组织炎症和肠道菌群的影响。方法将45只SD大鼠随机分为对照组、模型组和小檗碱处理组,每组15只。在模型组和小檗碱处理组,采用高脂饮食喂养诱导NAFLD模型。实验结束时取肝组织行病理学检查,取血清检测空腹血糖(FPG)和空腹胰岛素(FINS),计算胰岛素抵抗指数(IRI);采集粪便,采用16SrRNA序列分析法检测肠道菌群变化;采用ELISA法检测血清白细胞介素-6(IL-6)、IL-10和肿瘤坏死因子-α(TNF-α)水平。结果在高脂喂养16 w末,取2只动物肝组织检查,提示造模成功。在实验结束时,小檗碱处理组动物肝组织学病变明显改善;小檗碱处理组大鼠血清ALT、AST和LDL水平分别为(78.0±6.0)IU/L、(119.6±8.8)IU/L和(61.3±5.0)mg/dL,显著低于模型组【分别为(211.5±9.0)IU/L、(312.6±9.7)IU/L和(97.6±8.9)mg/dL,P<0.05】,而血清HDL水平为(70.0±5.4)mg/dL,显著高于模型组【(14.6±5.7)mg/dL,P<0.05】;小檗碱处理组FPG、FINS和IRI分别为(4.1±0.5)mmol/L、(12.7±0.9) mU/L和(2.8±0.4),显著低于模型组【分别为(5.9±0.9)mmol/L、(19.3±1.1)mU/L和(4.6±1.0),P<0.05】;小檗碱处理组大鼠肠道毛螺旋菌属和梭菌属水平分别为(5.6±0.5)和(2.0±0.4),显著低于模型组【分别为(13.4±1.3)和(7.2±0.6),P<0.05】,而瘤胃球菌和乳酸菌属水平分别为(2.4±0.5)和(2.9±0.5),显著高于模型组【分别为(1.0±0.2)和(1.1±0.2),P<0.05】;小檗碱处理组大鼠血清IL-6和TNF-α水平分别为(52.1±9.8)pg/mL和(70.0±17.3)pg/mL,显著低于模型组【分别为(80.3±21.6)pg/mL和(120.8±22.6)pg/mL,P<0.05】,而血清IL-10水平为(6.1±2.7)pg/mL,显著高于模型组[(3.4±1.8)pg/mL,P<0.05]。结论小檗碱可以通过调节肠道菌群改善NAFLD大鼠肝组织炎症反应,有效抑制细胞因子活动水平。

关键词: 非酒精性脂肪性肝病, 肝组织炎症, 小檗碱, 肠道菌群, 高脂饮食, 大鼠

Abstract: Objective The purpose of this experiment was to explore the effect of berberine (BBR) on liver inflammation reaction and intestinal flora changes in rats with non-alcoholic fatty liver disease (NAFLD). Methods Forty-five SD rats were randomly divided into control, model and and BBR-intervened groups, with 15 rats in each group. The NAFLD models were established by high-fat die feeding. The liver pathological changes was observed, and fasting blood glucose (FPG), fasting insulin (FINS) levels and insulin resistance index (IRI) were detected by automatic biochemical analyzer. The fecal 16SrRNA sequence were detected, and serum interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) levels were detected by ELISA. Results At the end of 16 week experiment, the NAFLD model was successfully established as proved in two rats; at the end of the experiment, the liver steatosis and inflammatory reactions improved greatly in BBR-intervened rats as compared to in the model; serum ALT, AST and LDL levels in the BBR-intervened group were (78.0±6.0)IU/L, (119.6±8.8)IU/L and (61.3±5.0)mg/dL, significantly lower than [(211.5±9.0)IU/L, (312.6±9.7)IU/L and (97.6±8.9)mg/dL, respectively, P<0.05], while serum HDL level was (70.0±5.4)mg/dL, significantly higher than [(14.6±5.7)mg/dL, P<0.05] in the model; the FPG, FINS and IRI in BBR-intervened group were (4.1±0.5)mmol/L, (12.7±0.9) mU/L and (2.8±0.4), significantly lower than [(5.9±0.9)mmol/L, (19.3±1.1)mU/L and (4.6±1.0), respectively, P<0.05] in model; the fecal Lachnospira and Clostridium in BBR-intervened group were (5.6±0.5) and (2.0±0.4), significantly lower than[(13.4±1.3) and (7.2±0.6), P<0.05], while the Ruminococci and Lactic acid bacteria were (2.4±0.5 and (2.9±0.5), significantly higher than [(1.0±0.2) and (1.1±0.2), P<0.05] in the model; serum IL-6 and TNF-α levels in BBR-intervened group were (52.1±9.8)pg/mL and (70.0±17.3)pg/mL, both significantly lower than [(80.3±21.6)pg/mL and (120.8±22.6)pg/mL, P<0.05], while serum IL-10 level was (6.1±2.7)pg/mL, significantly higher than [(3.4±1.8)pg/mL, P<0.05] in the model. Conclusion The BBR could alleviate hepatic inflammatory reactions in rats with high-fat diet-induced NAFLD, which might be related to the regulation of intestinal floras.

Key words: Non-alcoholic fatty liver diseases, Liver inflammation, Berberine, Intestinal flora, High-fat diet, Rats

黄淡霞, 招志辉, 萧月兴, 何艳青. 小檗碱通过调节肠道菌群改善高脂饮食诱导的非酒精性脂肪性肝病大鼠肝组织炎症实验研究^*[J]. 实用肝脏病杂志, 2023, 26(1): 23-26.

Huang Danxia, Zhao Zhihui, Xiao Yuexing, et al. Berberine improves liver injuries and intestinal flora disorders in high-fat diet-induced non-alcoholic fatty liver disease in rats[J]. Journal of Practical Hepatology, 2023, 26(1): 23-26.

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小檗碱通过调节肠道菌群改善高脂饮食诱导的非酒精性脂肪性肝病大鼠肝组织炎症实验研究^*

Berberine improves liver injuries and intestinal flora disorders in high-fat diet-induced non-alcoholic fatty liver disease in rats

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