The Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, St Lucia, Australia.
Equine Vet J. 2011 Jul;43(4):471-7. doi: 10.1111/j.2042-3306.2010.00292.x. Epub 2011 Jan 19.
The timing of lamellar basement membrane (BM) changes occurring during laminitis development is incompletely understood.
To determine the temporal progression of lamellar BM changes and whether laminin-332 (Ln-332) γ2 cleavage products are generated during laminitis development.
Eight clinically normal Standardbred horses were allocated into treatment (n = 5) or sham (n = 3) groups. The treatment group received, via nasogastric intubation, an oligofructose (OF) bolus (10 g/kg bwt) while the sham group was given water. Laminitis induction proceeded for 48 h followed by euthanasia. Lamellar biopsies were obtained prior to dosing and at intervals during the treatment period for analysis (at 12, 18, 24, 30 and 36 h and at 48 h following euthanasia).
Changes in lamellar collagen type IV and Ln-332 were first observed at 12 h post dosing. A unique pattern of reactivity for the Ln-332 γ2 antibody D4B5 occurred, in which reactivity was observed only in lamellar tissue affected by laminitis. No bioactive Ln-332 γ2 proteolytic fragments were detected in lamellar samples.
Basement membrane changes occurred early during the laminitis process. Direct Ln-332 γ2 cleavage to release biologically active products did not appear to occur. Thus loss of stability or protein interaction of the BM is probably responsible for the γ2 specific reactivity observed.
Basement membrane changes may a first step in lamellar failure occurring prior to detection with conventional methods. Thus, more sensitive detection methods of BM changes are required to study laminitis development.
不完全了解在蹄叶炎发展过程中发生的板层基底膜 (BM) 变化的时间进程。
确定板层 BM 变化的时间进程，以及在蹄叶炎发展过程中是否产生层粘连蛋白-332 (Ln-332) γ2 裂解产物。
将 8 匹临床正常的标准马分配到治疗（n = 5）或假手术（n = 3）组。治疗组通过鼻胃管给予低聚果糖 (OF) （10 g/kg bwt），而假手术组给予水。在安乐死后的 48 小时内进行蹄叶炎诱导。在给药前和治疗期间的各个时间点（在 12、18、24、30 和 36 小时以及安乐死后 48 小时）采集板层活检进行分析。
在给药后 12 小时首次观察到板层胶原 IV 和 Ln-332 的变化。对 Ln-332 γ2 抗体 D4B5 发生了一种独特的反应模式，仅在受蹄叶炎影响的板层组织中观察到反应。在板层样本中未检测到生物活性的 Ln-332 γ2 蛋白水解片段。
基底膜变化发生在蹄叶炎过程的早期。直接的 Ln-332 γ2 裂解以释放生物活性产物似乎没有发生。因此，BM 的稳定性或蛋白相互作用的丧失可能是导致观察到的 γ2 特异性反应的原因。
基底膜变化可能是在常规方法检测到之前，板层失效的第一步。因此，需要更敏感的 BM 变化检测方法来研究蹄叶炎的发展。
