Effect of limonin on liver fibrosis in rats and preliminary exploration of its mechanism

XIAO Yuhong; AN Zhenxiang

doi:10.6039/j.issn.1001-0408.2022.24.05

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Effect of limonin on liver fibrosis in rats and preliminary exploration of its mechanism

更新时间：2023-02-22

- Effect of limonin on liver fibrosis in rats and preliminary exploration of its mechanism
- ZHONGGUO YAOFANG Vol. 33, Issue 24, Pages: 2968-2972(2022)
- 作者机构：
  
  1.贵州中医药大学第一临床医学院，贵阳　550002
  2.贵州中医药大学第一附属医院消化内科，贵阳　550001
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2022.24.05
  CLC： R965
- Published：30 December 2022，
  
  Received：26 July 2022，
  
  Revised：19 November 2022，
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肖玉洪,安祯祥.柠檬苦素对大鼠肝纤维化的影响及机制初探 ^Δ[J].中国药房,2022,33(24):2968-2972.

XIAO Yuhong,AN Zhenxiang.Effect of limonin on liver fibrosis in rats and preliminary exploration of its mechanism[J].ZHONGGUO YAOFANG,2022,33(24):2968-2972.
肖玉洪,安祯祥.柠檬苦素对大鼠肝纤维化的影响及机制初探 ^Δ[J].中国药房,2022,33(24):2968-2972. DOI： 10.6039/j.issn.1001-0408.2022.24.05.

XIAO Yuhong,AN Zhenxiang.Effect of limonin on liver fibrosis in rats and preliminary exploration of its mechanism[J].ZHONGGUO YAOFANG,2022,33(24):2968-2972. DOI： 10.6039/j.issn.1001-0408.2022.24.05.

摘要

目的

探讨柠檬苦素对大鼠肝纤维化的影响及机制。

方法

将42只SD雄性大鼠随机分为正常组、模型组、阳性对照组（秋水仙碱0.1 mg/kg）和柠檬苦素低、高剂量组（12.5、50 mg/kg），正常组和模型组各9只，其余组各8只。除正常组外，采用四氯化碳构建肝纤维化模型。造模成功后，正常组及模型组灌胃水，其余各组灌胃相应药物，每日1次，持续4周。末次给药后，采用酶联免疫吸附测定法检测各组大鼠血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、透明质酸（HA）、层粘连蛋白（LN）含量；采用苏木精-伊红（HE）及Masson染色观察肝组织形态和肝纤维化变化；采用Western blot法检测肝组织中蛋白激酶B（Akt）、磷酸化Akt（p-Akt）、E-钙黏蛋白（E-cadherin）、波形蛋白（vimentin）蛋白表达水平，并计算p-Akt/Akt比值。

结果

与正常组比较，模型组大鼠血清ALT、AST、HA、LN含量均显著升高（

＜0.01），HE及Masson染色均观察到肝组织有大量纤维组织增生，肝组织中Akt、p-Akt、vimentin蛋白表达水平及p-Akt/Akt比值均显著升高（

＜0.01），E-cadherin蛋白表达水平显著降低（

＜0.01）。与模型组比较，柠檬苦素低、高剂量组大鼠肝组织的纤维增生程度均有所减轻，除柠檬苦素低剂量组的LN、E-cadherin指标外其余指标均显著逆转（

＜0.05或

＜0.01）。

结论

柠檬苦素能改善大鼠肝纤维化，作用机制可能与抑制Akt磷酸化及逆转上皮间质转化进程有关。

Abstract

OBJECTIVE

To explore the effect and mechanism of limonin on liver fibrosis in rats.

METHODS

Forty-two SD male rats were randomly divided into normal group， model group， positive control group （colchicine， 0.1 mg/kg）， low-dose group of limonin （12.5 mg/kg） and high-dose group of limonin （50 mg/kg）， with 9 rats in normal group and model group， and 8 rats in other groups. Except for normal group， the model of liver fibrosis was established by carbon tetrachloride. After modeling， normal group and model group were given distilled water intragastrically， and administration groups were given relevant medicine intragastrically，once a day，for consecutive 4 weeks. After the last medication， the serum contents of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， hyaluronic acid （HA） and laminin （LN） in rats were detected by enzyme-linked immunosorbent assay （ELISA） method. HE and Masson staining were used to observe the pathological changes and fibrotic change of liver tissue. Western blot assay was used to detect the protein expressions of protein kinase B （Akt）， phosphorylated-protein kinase B （p-Akt）， E-cadherin and vimentin in liver tissue； ratio of p-Akt/Akt was calculated.

RESULTS

Compared normal group， the serum contents of ALT， AST， HA and LN in rats were all increased significantly in model group （

＜0.01）； HE and Masson staining showed that a large number of fibrous tissue hyperplasia， protein expressions of Akt， p-Akt and vimentin as well as p-Akt/Akt ratio in liver tissue were significantly increased （

＜0.01）， while E-cadherin protein expression was significantly decreased （

＜0.01）. Compared with model group， the degree of fibrosis hyperplasia in liver tissue was relieved in high-dose group and low-dose group of limonin， and other indexes were all reversed significantly except for LN and E-cadherin in the low-dose group of limonin （

＜0.01 or

＜0.05）.

CONCLUSIONS

Limonin can improve liver fibrosis in rats， the mechanism of which may be related to the inhibition of Akt phosphorylation and reversal of epithelial-mesenchymal transition process.

关键词

柠檬苦素肝纤维化上皮间质转化大鼠

Keywords

liver fibrosisepithelial-mesenchymal transitionrat

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