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王宗玲, 卓怡云, 吕婧, 王子龙, 刘颖, 梁惠. 纳豆联合红曲对大鼠酒精性肝损伤改善作用及机制[J]. 中国公共卫生, 2019, 35(9): 1219-1224. DOI: 10.11847/zgggws1119890
引用本文: 王宗玲, 卓怡云, 吕婧, 王子龙, 刘颖, 梁惠. 纳豆联合红曲对大鼠酒精性肝损伤改善作用及机制[J]. 中国公共卫生, 2019, 35(9): 1219-1224. DOI: 10.11847/zgggws1119890
Zong-ling WANG, Yi-yun ZHUO, Jing LÜ, . Alleviating effect and mechanism of natto combined with red yeast rice on alcoholic liver injury in rats[J]. Chinese Journal of Public Health, 2019, 35(9): 1219-1224. DOI: 10.11847/zgggws1119890
Citation: Zong-ling WANG, Yi-yun ZHUO, Jing LÜ, . Alleviating effect and mechanism of natto combined with red yeast rice on alcoholic liver injury in rats[J]. Chinese Journal of Public Health, 2019, 35(9): 1219-1224. DOI: 10.11847/zgggws1119890

纳豆联合红曲对大鼠酒精性肝损伤改善作用及机制

Alleviating effect and mechanism of natto combined with red yeast rice on alcoholic liver injury in rats

  • 摘要:
      目的  探讨纳豆联合红曲对大鼠酒精性肝损伤(ALD)的改善作用及机制。
      方法  雄性Wistar大鼠随机分为4组:对照组(生理盐水);模型组(56°白酒6 mL/kg 1周+8 mL/kg 1周+10 mL/kg 1周+11 mL/kg 7周);纳豆红曲组(595.59 FU/kg纳豆激酶+4.46 mg/kg洛伐他汀+酒精);甘利欣组(200 mg/kg甘利欣+酒精),纳豆红曲与甘利欣组酒精剂量同模型组,连续10周。苏木精 – 伊红染色(HE)和透射电镜观察肝脏和小肠组织结构;测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)活性;酶联免疫吸附法(ELISA)检测血清内毒素水平;蛋白质印迹法(Western blot)检测肝组织白细胞分化抗原(CD14)、Toll样受体4(TLR4)和肿瘤坏死因子– α(TNF-α)蛋白表达水平。
      结果  与对照组比较,模型组大鼠肝和小肠组织均出现明显的病变损伤;与模型组比较,纳豆红曲和甘利欣组大鼠肝脏和小肠组织病理损伤明显改善。与对照组比较,模型组大鼠血清ALT、AST、GGT、ALP水平分别为(60.5 ± 15.4)、(152 ± 33.11)、(4.18 ± 0.75)、(157.3 ± 46.64)U/L明显升高(P < 0.05);与模型组比较,纳豆红曲组大鼠血清AST、GGT、ALP水平分别为(130.16 ± 27.66)、(3 ± 1.09)、(137 ± 24.77)U/L明显下降(P < 0.05)。与对照组比较,模型组大鼠血清内毒素水平升高,肝脏组织中CD14、TLR4、TNF-α 蛋白表达明显升高(P < 0.05);与模型组比较,纳豆红曲和甘利欣组大鼠内毒素水平明显下降(P < 0.05),肝组织中CD14、TLR4和TNF-α 蛋白表达均明显下降(P < 0.05)。
      结论  纳豆联合红曲对大鼠酒精性肝损伤具有一定的改善作用,其机制可能与纳豆红曲降低血清内毒素,下调肝组织CD14和TLR4蛋白表达,抑制下游TNF-α 释放,减轻肝脏损伤有关。

     

    Abstract:
      Objective  To explore alleviating effect and mechanism of natto combined with red yeast rice on alcoholic liver injury (ALD) in rats.
      Methods  Totally 48 male Wistar rats were randomly divided into four groups: a control group with normal saline; a model group gavaged with a liquor containing 56% alcohol at an increment dosage of 6, 8, and 10 ml/kg·bw·d continuously for 3 weeks and at a dosage of 11 ml/kg·bw·d for 7 weeks; a natto plus red yeast rice group gavaged with nattokinase at dosage of 595.59 FU/kg·bw·d and lovastatin at dosage of 4.46 mg/kg·bw·d one hour before the liquor treatment the same as the model group; and a diammonium glycyrrhizinate group gavaged with diammonium glycyrrhizinate at dosage of 200 mg/kg·bw·d one hour before the liquor treatment the same as the model. Structure of liver and small intestine tissue were observed with hematoxylin and eosin (HE) stain and transmission electron microscopy. Serum alanine aminotransferase (ALT) , aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) were detected with automatic biochemistry analyzer; serum endotoxin was determined with enzyme-linked immunosorbent assay (ELISA); protein expressions of cluster of differentiation-14 (CD14), Toll-like receptor 4 (TLR4) and tumor necrosis factor α (TNF-α) in liver tissues were detected with Western blot.
      Results  Compared with those of the control group, obvious pathological changes in liver and small intestine tissues of the model group were observed and the pathological changes were significantly alleviated in the natto plus red yeast rice group and diammonium glycyrrhizinate group in comparison with those of the model group. Compared with those of the control group, the serum ALT (60.50 ± 15.40 U/L), AST (152.00 ± 33.11 U/L) , GGT (4.18 ± 0.75 U/L) and ALP (157.30 ± 46.64 U/L) of the model group increased significantly (P < 0.05 for all); while, compared with those of the model group, the AST (130.16 ± 27.66 U/L), GGT (3.00 ± 1.09 U/L) and ALP (137.00 ± 24.77 U/L) of the natto plus red yeast rice group decreased significantly (all P < 0.05). Compared with those of the control group, serum endotoxin and expressions of CD14, TLR4 and TNF-α in liver tissues of the model group increased significantly (all P < 0.05); whereas, serum endotoxin and expressions of CD14, TLR4 and TNF-α in liver tissues of the natto plus red yeast rice group decreased significantly in comparison with those of the model group and the diammonium glycyrrhizinate group.
      Conclusion  Natto combined with red yeast rice could alleviate alcoholic liver injury by down-regulating serum endotoxin, expressions of CD14 and TLR4 protein in liver tissue and inhibiting the release of downstream TNF-α in rats.

     

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