Establishment of a transgenic sickle-cell mouse model to study the pathophysiology of priapism.
Establishment of a transgenic sickle-cell mouse model to study the pathophysiology of priapism.
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DOI：
10.1111/j.1743-6109.2009.01359.x
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Champion HC
中科院分区：
文献类型：
--
作者：
Bivalacqua TJ;Musicki B;Hsu LL;Gladwin MT;Burnett AL;Champion HC
阴茎异常勃起是一种了解甚少的疾病过程，很少有关于这种勃起障碍的病因学和病理生理学的信息。男性镰状细胞病患者是阴茎异常勃起的高发人群。建立转基因镰状细胞小鼠模型研究镰状细胞病相关性阴茎异常勃起的病理生理。使用表达人镰状血红蛋白的转基因镰状细胞病小鼠。使用三组小鼠：（i）野生型（WT），（ii）镰状细胞杂合子（Hemi），和（ii）镰状细胞纯合子（Sickle）。使用每组小鼠的两个年龄组：年轻成年（4-6个月）和老年（18-22个月）。测定WT、Hemi和Sickle小鼠阴茎的组织学（三色染色以测量胶原与平滑肌的比率）、阴茎羟脯氨酸含量（胶原含量）和透射电子显微镜分析，以及对海绵体神经刺激（CNS）的体内勃起反应[海绵体内压（ICP）的变化]。在每个实验组中，还测量了刺激前和刺激后的勃起反应频率（勃起次数/小时）。镰状小鼠阴茎中胶原与平滑肌的比例和羟脯氨酸含量与WT和Hemi小鼠阴茎相比增加（P < 0.05）。透射电镜下可见海绵窦平滑肌细胞束增厚，内皮细胞破坏，细胞膜小窝增多（P < 0.05）。与WT和Hemi小鼠勃起反应相比，镰状小鼠具有显著（P <0.05）更高的ICP至CNS，并且增加了CNS前后的勃起频率（P < 0.05）。随着年龄的增长，镰状小鼠确实发生了艾德（ICP对CNS的反应变化）。阴茎的形态变化和夸张的体内勃起反应支持使用这种转基因镰状细胞病动物模型来研究镰状细胞病相关的阴茎异常勃起的病理生理机制。
Priapism is a poorly understood disease process with little information on the etiology and pathophysiology of this erectile disorder. One group of patients with a high prevalence of priapism is men with sickle-cell disease. Establish an in vivo transgenic sickle-cell mouse model to study the pathophysiology of sickle-cell disease-associated priapism. Transgenic sickle-cell disease mice, expressing human sickle hemoglobin, were utilized. Three groups of mice were used: (i) wild type (WT), (ii) sickle-cell heterozygotes (Hemi), and (ii) sickle-cell homozygotes (Sickle). Two age groups of each cohort of mice were utilized: young adult (4–6 months) and aged (18–22 months). Histological (trichrome stain to measure ratio of collagen to smooth muscle), penile hydroxyproline content (collagen content), and transmission electron microscopic analysis of WT, Hemi, and Sickle mice penes, as well as in vivo erectile responses [change in intracavernous pressure (ICP)] to cavernous nerve stimulation (CNS), were determined. The frequency of erectile responses (erections/hour) pre- and poststimulation was also measured in each of the experimental groups. Sickle mice had increased (P < 0.05) collagen to smooth muscle ratio and hydroxyproline content in the penis when compared with WT and Hemi mice penes. Transmission electron microscopy demonstrated thickened smooth muscle cell bundles, disruption of the endothelial lining of the corporal sinusoids, and increased (P < 0.05) caveolae number. Sickle mice had significantly (P < 0.05) higher ICP to CNS and increased (P < 0.05) frequency of erections pre- and post-CNS when compared with WT and Hemi mice erectile responses. Sickle mice did develop ED (change in ICP in response to CNS) with increasing age. The morphometric changes of the penis and exaggerated in vivo erectile responses support the use of this transgenic sickle-cell disease animal model to study the pathophysiological mechanisms involved in sickle-cell disease-associated priapism.
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