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原文出自：Nutrition. 2005 Jul-Aug;21（7-8）:838-47.

　　最近，有文献报道了丁酸盐可以诱导细胞的分化或者凋亡，并且这种效应与脂肪氧化酶（LOX）以及环氧合酶（COX）有关，但是，关于丁酸盐对紧密连接的影响目前未见报道。人们已经知道，丁酸盐以及丙酸盐都可以通过他们对组蛋白去乙酰化酶的抑制作用从而引起组蛋白的乙酰化，并最终实现对基因转录的调控。在我们的研究中，我们研究了短链脂肪酸、丁酸盐、丙酸盐以及醋酸盐对肠上皮细胞间紧密连接通透性的影响，以及这种变化过程中LOX 和 COX的活化情况，并且研究了这些物质引起组蛋白乙酰化的可能机制。

　　实验者利用Caco-2细胞以及Transwell小室建立肠腔的体外模型，研究了几种LOX 、 COX抑制物质对紧密连接通透性的影响，以及对LOX 、COX mRNA水平的影响。同时，还研究了羟基二十碳四烯酸（这是一种LOX的催化产物）对TJ通透性的影响。在实验中，研究者还将几种短链脂肪酸的效应与曲古抑菌素A（一种组蛋白去乙酰化酶抑制剂）的效应进行了比较。

　　结果：使用LOX抑制剂能够明显的抑制丁酸盐所引起的紧密连接通透性的增加，而COX抑制剂则没有这种作用。丁酸盐能够增加细胞中LOX mRNA的表达水平，而羟基二十碳四烯酸以及曲古抑菌素A也都有类似的作用。

　　结论：以上结果表明，短链脂肪酸，尤其是丁酸盐，能够通过对组蛋白的乙酰化作用活化LOX，并且导致肠上皮细胞间紧密连接通透性的增加。

　　Short-chain fatty acids alter tight junction permeability in intestinal monolayer cells via lipoxygenase activation.

　　OBJECTIVE: Involvement of lipoxygenase （LOX） and cyclo-oxygenase （COX） on cellular differentiation or apoptosis induced by butyrate has been reported recently, but the effect on tight junction （TJ） permeability has not been reported. One major activity of butyrate and, to a lesser extent, propionate is to modulate gene transcription via histone acetylation by their histone deacetylase inhibitor activity. In this study, we evaluated the activation of LOX and COX in TJ permeability changes by short-chain fatty acids, butyrate, propionate, and acetate in intestinal monolayer cells and their possible mechanism by histone acetylation. METHODS: The effects of LOX and COX inhibitors on TJ permeability and the expression of LOX or COX mRNA induced by short-chain fatty acids were investigated in Caco-2 cells using Transwell chambers. The effects of hydroxyeicosatetraenoic acid （a product of LOX） on TJ permeability were also evaluated. The effects of short-chain fatty acids were compared with those of trichostatin A （histone deacetylase inhibitor）. RESULTS: A LOX inhibitor clearly inhibited the effect of butyrate on TJ permeability, whereas COX inhibitors did not. The LOX and COX inhibitors partly inhibited the effects of propionate but not of acetate. Butyrate increased LOX mRNA expression, and hydroxyeicosatetraenoic acid and trichostatin A mimicked its effect. CONCLUSION: These results suggest that short-chain fatty acids, especially butyrate, induce TJ permeability changes through LOX activation through histone acetylation.