The pig is a better model than the rabbit or rat for studying the pathophysiology of human mesenteric arteries
The pig is a better model than the rabbit or rat for studying the pathophysiology of human mesenteric arteries
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DOI：
10.1016/j.mvr.2023.104494
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发表时间：
2023-02-02
影响因子：
3.1
通讯作者：
Narvaez-Sanchez, Raul
中科院分区：
文献类型：
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作者：
Cupitra, Nelson Ivan;Leon-Rodriguez, Jimmy;Narvaez-Sanchez, Raul
目的：动物模型是研究心血管病理生理学和药理学的关键，但由于系统发育的多样性，有必要确定与人类血管结构最相似的模型。方法和结果：在本研究中，我们比较了人、猪、兔和大鼠肠系膜动脉的以下方面：1)α1和β2肾上腺素受体、M1、M2和M3受体、缓激肽(BKR)和血栓素-前列腺素(TP)受体的氨基酸序列的进化变化；ii)免疫荧光法评估α1、β2、M1、M3和TP受体在各膜中的表达；以及iii)通过进行器官浴试验，对受体依赖和非依赖的收缩激动剂和松弛药的反应性。在系统发育上，猪在进化上与人类的亲缘程度最高，而与人类、猪和大鼠相比，除了BKR外，兔子的进化差异最大。被测受体在猪的三层血管膜中的表达与人的表达最为相似。用单因素方差分析确定猪的血管反应性的差异，发现猪的血管反应性对KCl、苯肾上腺素、异丙肾上腺素和卡巴胆醇的敏感性(PD2)和最大效应(Emax)与人类最相似。结论：猪是一种比兔或大鼠更好的血管模型，可以用来推算人肠系膜动脉的结果。比较血管研究对理解不同物种的进化史具有重要意义。翻译观点：目前的发现有助于识别具有与人类相似的血管系统的动物模型。这些信息对于从动物模型到健康人或患病人更精确地推断动脉病理生理学或药理学的发现是重要的。
Aims: Animal models are essential to investigate cardiovascular pathophysiology and pharmacology, but phylogenetic diversity makes it necessary to identify the model with vasculature most similar to that of humans.Methods and results: In this study, we compared the mesenteric arteries of humans, pigs, rabbits and rats in terms of the i) evolutionary changes in the amino acid sequences of alpha 1 and beta 2 adrenoceptors; M1, M2, and M3 muscarinic receptors; and bradykinin (BKR) and thromboxane-prostanoid (TP) receptors, through bioinformatics tools; ii) expression of alpha 1, beta 2, M1, M3 and TP receptors in each tunica, as assessed by immunofluorescence; and iii) reactivity to receptor-dependent and independent contractile agonists and relaxants, by performing organ bath assays. Phylogenetically, pigs showed the highest degree of evolutionary closeness to humans for all re-ceptors, and with the exception of BKR, rabbits presented the greatest evolutionary difference compared to humans, pigs and rats. The expression of the measured receptors in the three vascular tunica in pigs was most similar to that in humans. Using a one-way ANOVA to determine the differences in vascular reactivity, we found that the reactivity of pigs was the most similar to that of humans in terms of sensitivity (pD2) and maximum effect of vascular reactivity (Emax) to KCl, phenylephrine, isoproterenol and carbachol.Conclusions: The pig is a better vascular model than the rabbit or rat to extrapolate results to human mesenteric arteries. Comparative vascular studies have implications for understanding the evolutionary history of different species.Translational perspective: The presented findings are useful for identifying an animal model with a vasculature that is similar to that of humans. This information is important to extrapolate, with greater precision, the findings in arterial pathophysiology or pharmacology from animal models to the healthy or diseased human being.