本文選題：組蛋白去乙酰化酶抑制劑 + FK��； 參考：《重慶醫(yī)科大學(xué)學(xué)報(bào)》2017年07期

【摘要】：目的:觀察組蛋白去乙�；敢种苿┝_米地辛(Romidepsin,FK228)對(duì)四氯化碳(carbon tetrachloride,CCl4)誘導(dǎo)小鼠肝纖維化模型的治療性作用,初步探討FK228對(duì)減輕小鼠肝纖維化的機(jī)制。方法:將30只8周齡C57BL/6雄性小鼠隨機(jī)分為對(duì)照組、造模組和治療組,每組10只;對(duì)照組腹腔注射生理鹽水;造模組腹腔注射10%CCl4溶液誘導(dǎo)肝纖維化,持續(xù)24周;治療組在誘導(dǎo)纖維化第20周開(kāi)始采用FK228進(jìn)行治療。檢測(cè)各組小鼠血清谷丙轉(zhuǎn)氨酶(alanine aminotransferase,ALT)、谷草轉(zhuǎn)氨酶(aspartate transaminase,AST)含量水平;對(duì)肝組織進(jìn)行HE染色和天狼星紅染色,觀察假小葉形態(tài)結(jié)構(gòu);進(jìn)行α-平滑肌肌動(dòng)蛋白(α-smooth muscle actin,α-SMA)免疫組化染色,觀察肝星狀細(xì)胞活化程度及肝纖維化進(jìn)程;Western blot半定量分析α-SMA蛋白在肝臟中的表達(dá)情況。結(jié)果:造模組血清ALT(67.270±11.109)IU/L,而治療組小鼠的血清ALT(37.670±8.461)IU/L顯著下降(P=0.019);肝組織切片HE染色和天狼星紅染色顯示造模組纖維化程度高、假小葉形成明顯,而治療組纖維化程度明顯減弱;免疫組化染色和Western blot結(jié)果顯示治療組α-SMA水平相對(duì)于造模組明顯降低(P=0.001)。結(jié)論:研究結(jié)果首次證實(shí)FK228對(duì)降低小鼠肝纖維化程度有治療性作用,而且其機(jī)制可能與抑制星狀細(xì)胞活化和降低α-SMA蛋白表達(dá)水平有關(guān)。
[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 偽 -smooth muscle actin (偽 -SMA) immunohistochemical staining was performed. The activation degree of hepatic stellate cells and the expression of 偽 -SMA protein in liver were studied by Western blot. Results: serum alt in model group was (67.270 鹵11.109) IUP / L, while serum alt in treatment group was (37.670 鹵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 偽 -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 偽 -SMA protein expression.
【作者單位】： 重慶醫(yī)科大學(xué)第二附屬醫(yī)院肝膽外科;重慶醫(yī)科大學(xué)感染性疾病分子生物學(xué)教育部重點(diǎn)實(shí)驗(yàn)室;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(編號(hào):81602045、81471946) 重慶市科學(xué)技術(shù)委員會(huì)資助項(xiàng)目(編號(hào):cstc2016jcyj A0206) 重慶醫(yī)科大學(xué)“優(yōu)秀青年學(xué)者”資助項(xiàng)目(編號(hào):CYYQ201503)
【分類(lèi)號(hào)】：R575.2

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