VISCOELASTIC PROPERTIES OF TUBULE BASEMENT-MEMBRANES IN EXPERIMENTAL RENAL CYSTIC-DISEASE

VISCOELASTIC PROPERTIES OF TUBULE BASEMENT-MEMBRANES IN EXPERIMENTAL RENAL CYSTIC-DISEASE
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DOI:
10.1038/ki.1987.191
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发表时间:
1987-08-01
影响因子:
19.6
通讯作者:
GARDNER, KD
GARDNER, KD
中科院分区:
医学1区
文献类型:
--
作者:
GRANTHAM, JJ;DONOSO, VS;GARDNER, KD

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遗传性和获得性肾囊肿是由逐渐增大的小管段发展而来的。我们测量了单个正常小管和囊肿周围的基底膜的变形能力,以确定囊肿是否可能通过响应正常或增加的经小管静水压力的异常变形基底膜的简单延伸而发展。通过微量吸管抽吸技术在体外测量单个小管和囊肿的变形性(cm/dyne),该技术将吸管内的负压与小管或囊肿壁被抽吸到吸管中的距离相关联。粘弹性蠕变确定从吸移管抽吸对膜变形的时间依赖性影响。显微解剖对照组和获得性(二苯基噻唑[大鼠]、去甲二氢愈创木酸[大鼠])、遗传性(C57 BL/6 J [cpk/cpk]小鼠)和自发性(CFWw小鼠)肾囊肿疾病动物的近端和集合小管、肾小球囊和囊肿。由于胶原酶破坏了小管和囊壁的弹性,变形的主要阻力位于基底膜。在喂食DPT的动物中,通过电子显微镜观察,邻近囊肿的肾小管基底膜出现异常,但变形性和粘弹性蠕变的测量结果显示,在任何动物模型中,正常和囊性肾小管之间均无差异。囊肿的变形性值(7.7 ±. 1.1,10.9 .+-。1.1,11.2 .+-。0.6,9.4 ±。0.8. times. 10-3 DPT、NDGA、C57 BL/6 J和CFWw中分别为cm/dyne)与以下解释一致:如果囊肿是通过继发于跨上皮静水压力梯度的基底膜简单拉伸形成的,则需要39至134 cm H2O的高跨小管压力。由于在体内测量跨囊壁的静水压力不够高,我们得出结论,囊肿不扩大,由于增加变形性的小管基底膜。
Hereditary and acquired renal cysts develop from tubule segments that enlarge progressively. We measured the deformability of basement membranes surrounding individual normal tubules and cysts to determine if cysts might develop by simple extension of abnormally-deformable basement membrane in response to normal or increased transtubule hydrostatic pressures. Deformability (cm/dyne) was measured in individual tubules and cysts in vitro by a micropipet aspiration technique that related negative pressure within the pipet to the distance the tubule or cyst wall was aspirated into the pipet. Viscoelastic creep was determined from the time-dependent effect of pipet aspiration on membrane deformation. Proximal and collecting tubules, glomerular capsules and cysts were microdissected from controls and animals with acquired (Diphenylthiazole [rats], Nordihydroguaiaretic acid [rats]), hereditary (C57 BL/6J [cpk/cpk] mice) and spontaneous (CFWw mice) renal cystic diseases. The major resistance to deformation was localized to the basement membrane since collagenase destroyed the elasticity of tubule and cyst walls. Tubule basement membranes adjacent to cysts appeared abnormal by electron microscopy in the animals fed DPT, but measurements of deformability and viscoelastic creep showed no differences between normal and cystic tubules in any animal model. Deformability values of cysts (7.7 .+-. 1.1, 10.9 .+-. 1.1, 11.2 .+-. 0.6, 9.4 .+-. 0.8 .times. 10-3 cm/dyne in DPT, NDGA, C57 BL/6J and CFWw, respectively) are consistent with the interpretation that high transtubule pressures ranging from 39 to 134 cm H2O would be required if cysts form by simple stretching of the basement membrane secondary to a transepithelial hydrostatic pressure-gradient. Since in vivo measurements of hydrostatic pressures across cyst walls are not high enough we conclude that cysts do not enlarge due to increased deformability of tubule basement membranes.