Cline W S, Lorenzsonn V, Benz L, Bass P, Olsen W A
J Clin Invest. 1976 Aug;58(2):380-90. doi: 10.1172/JCI108482.
The mechanism of hydroxy fatty acid-induced secretion was investigated in perfused hamster small intestine in vivo. Sodium ricinoleate at an 8-mM concentration resulted in not only secretion of water and sodium, but an increase in intestinal clearance of inulin and a 16,000 mol wt dextran as well. A concentration of ricinoleate (2 mM) which did not affect water transport, however, did not alter intestinal permeability. Ricinoleate-induced intestinal secretion was also accompanied by increased mucosal cell exfoliation as measured by the appearance of DNA in the perfusate and by apparent injury to epithelial cell membranes as judged by measurement of sucrase activity and phospholipid in cell-free aliquots of luminal fluid. Light and electron microscopic studies demonstrated substantial mucosal architectural changes with 8 mM ricinoleate with villus shortening and injury to epithelial cells at the villus tips. In contrast, cholera enterotoxin caused marked secretion of sodium and water, presumably by a cyclic AMP mechanism, but did not alter inulin clearance or enhance DNA or sucrase appearance in the lumen. These studies suggest that at least a component of ricinoleate-induced intestinal secretion is related to structural alterations of the mucosa.
在体内灌注的仓鼠小肠中研究了羟基脂肪酸诱导分泌的机制。8 mM浓度的蓖麻油酸钠不仅导致水和钠的分泌,还使菊粉和16,000分子量葡聚糖的肠道清除率增加。然而,2 mM浓度的蓖麻油酸钠不影响水的转运,也不会改变肠道通透性。蓖麻油酸钠诱导的肠道分泌还伴随着粘膜细胞脱落增加,这可通过灌注液中DNA的出现来衡量,并且通过测定腔液无细胞等分试样中的蔗糖酶活性和磷脂来判断上皮细胞膜有明显损伤。光学和电子显微镜研究表明,8 mM蓖麻油酸钠会导致粘膜结构发生显著变化,出现绒毛缩短以及绒毛尖端上皮细胞损伤。相比之下,霍乱肠毒素可引起钠和水的显著分泌,推测是通过环磷酸腺苷机制,但不会改变菊粉清除率,也不会增加肠腔中DNA或蔗糖酶的出现。这些研究表明,蓖麻油酸钠诱导的肠道分泌至少有一部分与粘膜的结构改变有关。