von Engelhardt W
Physiologisches Institut der Tierärztlichen Hochschule Hannover.
Dtsch Tierarztl Wochenschr. 2005 Nov;112(11):413-7.
Short-chain fatty acids (SCFA) are present in hindgut contents in high concentrations. SCFA are generated and also absorbed rapidly in the large intestine. Absorption results from diffusion of the undissociated and lipid soluble form or in exchange for bicarbonate. The controversial concepts concerning the extent of diffusion or the exchange for bicarbonate are partly due to contradictory findings and unequal mechanisms in different species and in different segments of the large intestine as well as in the different methods used. An almost neutral pH microclimate at the luminal surface is of importance for absorption of SCFA. The apical membranes of the epithelial cells in caecum and in proximal colon of guinea pigs are an substantial barrier for the diffusion of SCFA. After withdrawal of butyrate for only one hour from the perfusion or incubation solutions a massive apoptosis had been observed during the in situ perfusion of segments of guinea pig large intestine and also in in vitro studies with isolated epithelia in Ussing-chambers. In vitro apoptotic bodies and cells are emitted at the epithelial surface. However, in vivo induced by butyrate deprivation resident macrophages were tightly clustered below the surface epithelium. Aided by cytoplasmatic projections these macrophages phagocytose and transport apoptotic material from the epithelial intercellular spaces into their bodies. Obviously macrophages can be overloaded by this massive apoptosis, and some of the undigested apoptotic fragments are emitted into the lamina propria. Formation of a colitis ulcerosa may originate from these released undigested apoptotic bodies. Furthermore hints indicate aetiological interrelations between deprivation of butyrate and colon cancer. Butyrate-paradox denotes the contrarian effects on apoptosis and cell proliferation after addition or deprivation of butyrate in cultures of large intestinal tumour-cell-lines in comparison with the healthy, intact epithelium.
短链脂肪酸(SCFA)在肠道后段内容物中浓度很高。SCFA在大肠中生成且吸收迅速。吸收是通过未解离的脂溶性形式的扩散或与碳酸氢根交换实现的。关于扩散程度或与碳酸氢根交换的争议性概念,部分是由于不同物种、大肠不同节段以及所采用的不同方法中存在相互矛盾的发现和不同的机制。肠腔表面近乎中性的pH微环境对SCFA的吸收很重要。豚鼠盲肠和近端结肠上皮细胞的顶端膜对SCFA的扩散是一个重要屏障。从灌注或孵育溶液中仅去除丁酸一小时后,在豚鼠大肠段的原位灌注过程中以及在Ussing室中对分离上皮的体外研究中,都观察到了大量细胞凋亡。体外凋亡小体和细胞从上皮表面排出。然而,在体内,丁酸剥夺诱导的驻留巨噬细胞紧密聚集在表面上皮下方。这些巨噬细胞借助细胞质突起吞噬并将上皮细胞间隙中的凋亡物质转运到它们体内。显然,巨噬细胞可能会因这种大量凋亡而不堪重负,一些未消化的凋亡碎片会排放到固有层中。溃疡性结肠炎的形成可能源于这些释放的未消化凋亡小体。此外,有迹象表明丁酸剥夺与结肠癌之间存在病因学上的相互关系。丁酸悖论是指与健康完整的上皮相比,在大肠肿瘤细胞系培养物中添加或剥夺丁酸后,对细胞凋亡和细胞增殖产生的相反影响。