Experimental study of romidepsin in reducing liver cirrhosis

Li Menghui; Zhou Hengyu; Liu Dina; Cai Ying; Gong Jianping; Tang Ni; Huang Ailong; Xia Jie

doi:10.13406/j.cnki.cyxb.001347

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Experimental study of romidepsin in reducing liver cirrhosis

更新时间：2024-01-17

- Experimental study of romidepsin in reducing liver cirrhosis
- Journal of Chongqing Medical University Vol. 42, Issue 7, Pages: 833-837(2017)
- 作者机构：
  
  1. 重庆医科大学第二附属医院肝胆外科
  2. 重庆医科大学感染性疾病分子生物学教育部重点实验室
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.001347
  CLC： R575.2
- Published：2017，
扫描看全文
Li Menghui, Zhou Hengyu, Liu Dina, et al. Experimental study of romidepsin in reducing liver cirrhosis. [J]. Journal of Chongqing Medical University 42(7):833-837(2017)
DOI：

Li Menghui, Zhou Hengyu, Liu Dina, et al. Experimental study of romidepsin in reducing liver cirrhosis. [J]. Journal of Chongqing Medical University 42(7):833-837(2017) DOI： 10.13406/j.cnki.cyxb.001347.

摘要

目的:观察组蛋白去乙酰化酶抑制剂罗米地辛(Romidepsin

FK228)对四氯化碳(carbon tetrachloride

CCl4)诱导小鼠肝纤维化模型的治疗性作用

初步探讨FK228对减轻小鼠肝纤维化的机制。方法:将30只8周龄C57BL/6雄性小鼠随机分为对照组、造模组和治疗组

每组10只;对照组腹腔注射生理盐水;造模组腹腔注射10%CCl4溶液诱导肝纤维化

持续24周;治疗组在诱导纤维化第20周开始采用FK228进行治疗。检测各组小鼠血清谷丙转氨酶(alanine aminotransferase

ALT)、谷草转氨酶(aspartate transaminase

AST)含量水平;对肝组织进行HE染色和天狼星红染色

观察假小叶形态结构;进行α-平滑肌肌动蛋白(α-smooth muscle actin

α-SMA)免疫组化染色

观察肝星状细胞活化程度及肝纤维化进程;Western blot半定量分析α-SMA蛋白在肝脏中的表达情况。结果:造模组血清ALT(67.270±11.109)IU/L

而治疗组小鼠的血清ALT(37.670±8.461)IU/L显著下降(P=0.019);肝组织切片HE染色和天狼星红染色显示造模组纤维化程度高、假小叶形成明显

而治疗组纤维化程度明显减弱;免疫组化染色和Western blot结果显示治疗组α-SMA水平相对于造模组明显降低(P=0.001)。结论:研究结果首次证实FK228对降低小鼠肝纤维化程度有治疗性作用

而且其机制可能与抑制星状细胞活化和降低α-SMA蛋白表达水平有关。

Abstract

Objective:To observe the effect of histone deacetylase inhibitor romidepsin（FK228）on liver cirrhosis in mice

and to investigate the underlying mechanism of renoprotective effect of FK228. Methods:Thirty experimental mice were randomly divided into three groups:control group（group A）

model group（group B）and treatment group（group C）. To set up the liver cirrhosis model

mice in group B and C were treated with intraperitoneal injection of CCl4 for 24 weeks. From the 21 th week

group C were treated with intraperitoneal injection of FK228 weekly. The levels of serum ALT and AST were detected to judge liver damage degree. HE and sirius red staining were used to observe pseudolobuli and tubercle. Immunohistochemical staining and Western blot analysis were used to detect the expression of osteopontin α-smooth muscle actin（α-SMA）in liver. Results:The data showed the average serum ALT in group C was（37.670±8.461）IU/L and（67.270±11.109）IU/L in group B. It was significantly decreased when treating the experimental mice with FK228（P=0.019）. Also

HE and sirius red staining revealed the degree of liver fibrosis in group C were weakened obviously. Additionally

Western blot and immunohistochemistry indicated the levels of α-SMA in group C were notable reduced（P=0.001）. Conclusion:The preventive effect of FK228 treatment for liver cirrhosis and the mechanism may involve down regulating levels of α-SMA and inhibition of HSC activation.

关键词

组蛋白去乙酰化酶抑制剂FK228肝纤维化α-平滑肌肌动蛋白

Keywords

Histone deacetylase inhibitorFK228liver fibrosisα-smooth muscle actin

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