Farmer R C, Tweedie J, Maslin S, Reber H A, Adler G, Kern H
Dig Dis Sci. 1984 Aug;29(8):740-51. doi: 10.1007/BF01312948.
We studied the changes in permeability and morphology in the main pancreatic duct of cats after exposure of the duct to specific bile salts. Cats were anesthetized and the main pancreatic duct was cannulated in the tail and head of the pancreas. The duct was perfused with sodium cholate (1, 1.5, 2, 15 mM) or sodium glycodeoxycholate (1, 2, 15 mM) for 60 min at pressures which never exceeded 20 cm water. Then the duct was perfused with fluorescein-tagged dextran molecules of specific size (3000, 20,000, or 40,000 daltons). Recovery of the dextran from portal venous blood indicated that the duct was permeable to that particular dextran. Normally the ducts were impermeable to even the 3000-dalton dextran, and perfusion with either 1 mM cholate or glycodeoxycholate did not change this. However, perfusion with either bile salt at concentrations above 1 mM progressively increased duct permeability. At this highest bile salt concentrations used, the ducts became permeable to molecules as large as 20,000 daltons. Morphologic changes paralleled the changes in permeability. Control animals had pancreatic ducts whose ultrastructure was indistinguishable from normal. Perfusion of the ducts with low concentrations of bile salt for up to 60 min resulted only in a loss of microvilli from the cell surface and an increase in cytoplasmic phagolysosomes. Perfusion with higher concentrations of bile salt for 5-60 min induced progressively severe alterations. These included disruption of the tight junctions and the swelling of intercellular spaces between the duct cells, flattening of the duct epithelium, and eventual cell loss which left a break in the epithelial lining of the duct. These studies indicate that the pancreatic duct in cats, exposed to specific bile salts at physiological concentrations and pressures, undergoes marked structural alterations. The duct becomes permeable to molecules at least as large as 20,000 daltons, whereas it is normally impermeable to molecules as small as 3000 daltons.
我们研究了猫的主胰管在暴露于特定胆汁盐后其通透性和形态的变化。将猫麻醉，然后在胰腺的尾部和头部插入主胰管插管。在压力不超过20厘米水柱的情况下，用胆酸钠（1、1.5、2、15毫摩尔）或甘氨脱氧胆酸钠（1、2、15毫摩尔）灌注胰管60分钟。然后用特定大小（3000、20000或40000道尔顿）的荧光素标记葡聚糖分子灌注胰管。门静脉血中葡聚糖的回收表明胰管对该特定葡聚糖具有通透性。正常情况下，胰管即使对3000道尔顿的葡聚糖也不通透，用1毫摩尔胆酸盐或甘氨脱氧胆酸盐灌注并不会改变这一情况。然而，用浓度高于1毫摩尔的任何一种胆汁盐灌注会逐渐增加胰管的通透性。在使用的最高胆汁盐浓度下，胰管对高达20000道尔顿的分子变得通透。形态学变化与通透性变化平行。对照动物的胰管超微结构与正常无异。用低浓度胆汁盐灌注胰管长达60分钟仅导致细胞表面微绒毛丧失以及细胞质吞噬溶酶体增加。用较高浓度胆汁盐灌注5 - 60分钟会逐渐引起更严重的改变。这些改变包括紧密连接的破坏、导管细胞间细胞间隙的肿胀、导管上皮的扁平化以及最终的细胞丢失，从而使导管上皮内衬出现破损。这些研究表明，猫的胰管在生理浓度和压力下暴露于特定胆汁盐时会发生明显的结构改变。胰管对至少高达20000道尔顿的分子变得通透，而正常情况下对小至3000道尔顿的分子是不通透的。
