發布時間：2022-06-12
來源：浩華生物
瀏覽量：132
選自：
毒理學與應用藥理學，第276卷，第2期，2014年4月15日，第129-135頁
Highlights 亮點
Tributyrin is a chemopreventive agent for rat colon aberrant crypt foci.
三丁酸甘油酯是大鼠結腸異常隱窩灶的化學預防劑。
Tributyrin increased apoptosis in an experimental rat colon carcinogenesis model.三丁酸甘油酯在實驗性大鼠結腸癌發生模型中增加了細胞凋亡。
Tributyrin treatment in a rat colon carcinogenesis model decreased DNA damage.在大鼠結腸癌發生模型中使用三丁酸甘油酯治療可減少DNA損傷。
Tributyrin treatment induced H3K9 acetylation in a rat colon carcinogenesis model.
三丁酸甘油酯可以治療在大鼠結腸癌發生模型中誘導H3K9乙?；?。
PS：高乙?；降?/font>H3K9 / K14（H3K9 / K14Ac）是染色體解聚的表觀遺傳標記和活躍轉錄的明顯信號。
Abstract 摘要
The chemopreventive activity of the histone deacetylase inhibitor (HDACi) tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of colon carcinogenesis.
在結腸癌發生的大鼠模型中評估了組蛋白去乙?；敢种苿?/font>HDACi）三丁酸甘油酯（TB）（丁酸的前體物）的化學預防活性。
The animals were treated with TB (TB group: 200 mg/100 g of body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100 g b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week.
分別給予TB (TB組：200 mg/100 g體重)或麥芽糊精(MD等熱量對照組：300 mg/100 g體重)治療，連續9周。在治療的第3周和第4周，TB組和MD組每周給予DMH (40 mg/kg 體重)兩次。
DMH：二甲基肼，誘變劑，科學實驗中用于誘導結腸癌。
After 9 weeks, the animals were euthanized, and the distal colon was examined. Compared with the control group (MD group), TB treatment reduced the total number of aberrant crypt foci (ACF; p<0.05) as well as the ACF with ≥ 4 crypts (p<0.05), which are considered more aggressive, but not inhibited the formation of DMH-induced O6-methyldeoxyguanosine DNA adducts.
9周后，對動物實施安樂死，并檢查遠端結腸。與對照組（MD組）相比，TB治療顯著減少了異常隱窩灶的總數（ACF；p<0.05）以及減少被認為更具有攻擊性的≥4個隱窩的異常隱窩灶（p<0.05），但并不抑制DMH誘導的脫氧鳥苷DNA加合物的形成。
PS：異常隱窩灶（ACF）被認為是結腸癌發生模型中最早可識別的腫瘤性病變。
The TB group also showed a higher apoptotic index (p<0.05) and reduced DNA damage (p<0.05) compared with MD group. TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of histone H3K9 acetylation compared with the MD group (p<0.05).
與MD組相比，TB組凋亡指數升高(p<0.05)， DNA損傷降低(p<0.05)。TB作為HDACi, BA前體物質組大鼠組蛋白H3K9乙?；礁哂?/font>MD組(p<0.05)。
PS：通過測定腫瘤細胞的凋亡指數來評估腫瘤細胞死亡率。
TB administration resulted in increased colonic tissue concentrations of BA (p<0.05) compared with the control animals.
與對照動物相比，TB給藥導致結腸組織中丁酸濃度升高（p<0.05）。
These results suggest that TB can be considered a promising chemopreventive agent for colon carcinogenesis because it reduced the number of ACF, including those that were more aggressive. Induction of apoptosis and reduction of DNA damage are cellular mechanisms that appear to be involved in the chemopreventive activity of TB.
這些結果表明，三丁酸甘油酯可以被認為是一種有希望的化學預防結腸癌的物質，因為它減少了ACF的數量，包括那些具攻擊性的ACF數量。誘導細胞凋亡和減少DNA損傷似乎是三丁酸甘油酯的化學預防作用的細胞機制。
組蛋白去乙?；?/font>(histone deacetylase,HDAC)是一類蛋白酶,對染色體的結構修飾和基因表達調控發揮著重要的作用。一般情況下，組蛋白的乙?；欣?/font>DNA與組蛋白八聚體的解離，核小體結構松弛，從而使各種轉錄因子和協同轉錄因子能與DNA結合位點特異性結合，激活基因的轉錄。而組蛋白的去乙?；瘎t發揮相反的作用。
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