组蛋白去乙酰化酶抑制剂FK228治疗小鼠肝硬化的实验研究

发布时间：2018-06-23 03:45

本文选题：组蛋白去乙酰化酶抑制剂 + FK　；参考：《重庆医科大学学报》2017年07期

【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]:Aim: to observe the therapeutic effect of Romidepsinin FK228, an inhibitor of histone deacetylase, on carbon tetrachloride CCl4 induced liver fibrosis in mice, and to explore the mechanism of FK228 in alleviating liver fibrosis in mice. Methods: thirty 8-week-old C57BL / 6 male mice were randomly divided into control group (n = 10), model group (n = 10) and treatment group (n = 10). The treatment group was treated with FK 228 at 20 weeks after fibrosis induction. The levels of serum alanine aminotransferase (alt) and aspartate transaminase (aspartate transaminase) were measured, the liver tissues were stained with HE and Sirius red to observe the morphology of pseudolobules, and 伪 -smooth muscle actin (伪 -SMA) immunohistochemical staining was performed. The activation degree of hepatic stellate cells and the expression of 伪 -SMA protein in liver were studied by Western blot. Results: serum alt in model group was (67.270 卤11.109) IUP / L, while serum alt in treatment group was (37.670 卤8.461) IUP / L (P < 0.019), liver tissue HE staining and Sirius red staining showed that the fibrosis degree of model group was higher than that of control group, but the fibrosis degree of treatment group was significantly decreased. Immunohistochemical staining and Western blot showed that 伪 -SMA level in the treatment group was significantly lower than that in the model group (P0. 001). Conclusion: FK228 has a therapeutic effect on decreasing the degree of liver fibrosis in mice, and its mechanism may be related to the inhibition of activation of stellate cells and the reduction of 伪 -SMA protein expression.
【作者单位】：重庆医科大学第二附属医院肝胆外科;重庆医科大学感染性疾病分子生物学教育部重点实验室;
【基金】：国家自然科学基金资助项目(编号:81602045、81471946) 重庆市科学技术委员会资助项目(编号:cstc2016jcyj A0206) 重庆医科大学“优秀青年学者”资助项目(编号:CYYQ201503)
【分类号】：R575.2

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