Pavelka M, Gangl A
Gastroenterology. 1983 Mar;84(3):544-55.
The involvement of microtubules in the transepithelial transport of exogenous lipid in intestinal absorptive cells has been suggested. Using electronmicroscopic, biochemical, and radiochemical methods, we have studied the effects of the antimicrotubular agent colchicine on the intestinal mucosa and on the intestinal transport of endogenous lipid of rats in the fasting state. After colchicine treatment, the concentration of triglycerides in intestinal mucosa of rats fasted for 24 h doubled, and electron microscopic studies showed a striking accumulation of lipid particles in absorptive epithelial cells of the tips of jejunal villi. These findings suggest that colchicine interferes with the intestinal transepithelial transport of endogenous lipoproteins. Additional studies, using an intraduodenal pulse injection of [14C]linoleic acid, showed that colchicine does not affect the uptake of fatty acids by intestinal mucosa. However, it had divergent effects on fatty acid esterification, enhancing their incorporation into triglycerides relative to phospholipids, and caused a significant accumulation of endogenous diglycerides, triglycerides, and cholesterol esters within the absorptive intestinal epithelium. Detailed ultrastructural and morphometric studies revealed a decrease of visible microtubules, and a displacement of the smooth and rough endoplasmic reticulum and Golgi apparatus. Furthermore, it is shown that after colchicine treatment, microvilli appear at the lateral plasma membrane of intestinal absorptive cells, a change not previously reported to our knowledge. Thus, our study shows that (a) colchicine causes significant changes in enterocyte ultrastructure and (b) colchicine perturbs the reesterification of absorbed endogenous fatty acids and their secretion in the form of triglyceride-rich lipoproteins from the enterocyte.
已有研究表明微管参与肠道吸收细胞中外源性脂质的跨上皮运输。我们使用电子显微镜、生化和放射化学方法，研究了抗微管药物秋水仙碱对禁食状态下大鼠肠黏膜及内源性脂质肠道转运的影响。秋水仙碱处理后，禁食24小时大鼠肠黏膜中甘油三酯的浓度翻倍，电子显微镜研究显示空肠绒毛顶端吸收上皮细胞中脂质颗粒显著积聚。这些发现表明秋水仙碱干扰内源性脂蛋白的肠道跨上皮运输。使用十二指肠脉冲注射[14C]亚油酸的进一步研究表明，秋水仙碱不影响肠黏膜对脂肪酸的摄取。然而，它对脂肪酸酯化有不同影响，相对于磷脂，增强了脂肪酸掺入甘油三酯的过程，并导致吸收性肠上皮细胞内源性甘油二酯、甘油三酯和胆固醇酯显著积聚。详细的超微结构和形态计量学研究显示可见微管减少，滑面内质网和粗面内质网以及高尔基体移位。此外，研究表明秋水仙碱处理后，肠吸收细胞的侧质膜出现微绒毛，据我们所知，这一变化此前未见报道。因此，我们的研究表明：（a）秋水仙碱导致肠上皮细胞超微结构发生显著变化；（b）秋水仙碱扰乱吸收的内源性脂肪酸的再酯化及其以富含甘油三酯的脂蛋白形式从肠上皮细胞分泌。
