高胰岛素血症增加马的趾血管阻力和内皮素-1 的表达。
Hyperinsulinaemia increases vascular resistance and endothelin-1 expression in the equine digit.
机构信息
Clinic of Orthopaedics in Large Animals, Department of Horses and Small Animals, Vienna University of Veterinary Medicine, Austria.
出版信息
Equine Vet J. 2013 Sep;45(5):613-8. doi: 10.1111/evj.12040. Epub 2013 Mar 12.
REASONS FOR PERFORMING STUDY
Insulin leads to overexpression of endothelin-1 (ET-1) in the endothelium of insulin-resistant rodents. If this is also the case in equine laminar tissue, this could explain the predisposition of insulin-resistant horses to laminitis.
OBJECTIVES
To investigate the effect of hyperinsulinaemia on metabolism and vascular resistance of the isolated equine digit in a model of extracorporeal perfusion.
STUDY DESIGN
Randomised, controlled study with interventional group, with blinded evaluation of histology results.
METHOD
After exsanguination, equine digits (n = 11) and autologous blood were collected at an abattoir. One digit served as a hyperinsulinaemic pilot limb, 5 digits were assigned to the hyperinsulinaemic perfusion (IP) group and 5 to the control perfusion (CP) group. Digits were perfused for 10 h at a defined perfusion rate of 12 ml/min/kg. After the first hour of perfusion (equilibration period), insulin was added to the reservoir of the IP digits. Perfusion pressure, glucose consumption, lactate and lactate dehydrogenase were monitored. Vascular resistance was calculated as perfusion pressure (in millimetres of mercury) in relation to the flow rate (in millilitres per minute). After perfusion, histology samples of the dorsal hoof wall (haematoxylin & eosin or periodic acid-Schiff) were evaluated. Immunohistology with a polyclonal rabbit-derived anti-endothelin antibody was used for detection of ET-1.
RESULTS
In the IP group, the mean insulin concentration in the plasma of the perfusate was 142 ± 81 μiu/ml, while insulin concentration was <3 μiu/ml in the CP group. Mean vascular resistance was significantly higher (P<0.01) in the IP group (2.04 ± 1.13 mmHg/ml/min) than in the CP group (1.31 ± 0.55 mmHg/ml/min). Histology of the IP group samples showed significantly more vessels with an open lumen, increased width of the secondary epidermal lamellae and formation of oedema. In the lamellar vessels (veins and arteries) and nerve fibres, ET-1 expression was much more prominent in the IP group than in the CP group samples.
CONCLUSIONS
Short-term hyperinsulinaemia leads to increased vascular resistance in the equine digit and increased expression of ET-1 in the laminar tissue.
研究目的
胰岛素可导致胰岛素抵抗啮齿动物的内皮细胞中内皮素-1（ET-1）过度表达。如果马的层状组织也是如此，这可能可以解释胰岛素抵抗的马易患蹄叶炎的原因。
研究目的
在离体灌注模型中，研究高胰岛素血症对分离的马指（digit）代谢和血管阻力的影响。
研究设计
随机、对照研究，实验组，组织学结果盲法评估。
方法
在屠宰场采集马指（n=11）和自体血。一个指用作高胰岛素血症的试验肢体，5 个指分配到高胰岛素灌注（IP）组，5 个指分配到对照灌注（CP）组。在 12ml/min/kg 的规定灌注速度下，指灌注 10 小时。灌注 1 小时后（平衡期），将胰岛素加入 IP 指的储液器中。监测灌注压、葡萄糖消耗、乳酸和乳酸脱氢酶。血管阻力作为灌注压（毫米汞柱）与流量（毫升/分钟）的比值计算。灌注后，评估背侧蹄壁的组织学样本（苏木精和伊红或过碘酸希夫染色）。使用多克隆兔源性抗内皮素抗体进行免疫组织化学检测以检测 ET-1。
结果
在 IP 组中，灌注液中血浆胰岛素浓度的平均值为 142±81μiu/ml，而 CP 组中胰岛素浓度<3μiu/ml。IP 组的平均血管阻力显著升高（P<0.01）（2.04±1.13mmHg/ml/min），CP 组为（1.31±0.55mmHg/ml/min）。IP 组样本的组织学显示，开放腔的血管明显更多，次级表皮板的宽度增加，并且形成水肿。在层状血管（静脉和动脉）和神经纤维中，IP 组样本中 ET-1 的表达明显高于 CP 组。
结论
短期高胰岛素血症可导致马指血管阻力增加，层状组织中 ET-1 表达增加。
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