大鼠皮下模型中同种异体主动脉壁的钙化。病理生理学以及Al3+和氨基二膦酸盐预孵育的抑制作用。

Calcification of allograft aortic wall in a rat subdermal model. Pathophysiology and inhibition by Al3+ and aminodiphosphonate preincubations.

作者信息

Webb C L, Nguyen N M, Schoen F J, Levy R J

机构信息

Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor 48109-0576.

出版信息

Am J Pathol. 1992 Aug;141(2):487-96.

PMID:1497095

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1886611/

Abstract

Aortic allograft conduits and valves frequently undergo calcific degeneration. To study this problem, a rat subdermal model of nonvalved aortic wall allograft calcification was characterized, and experimental studies were carried out to test the hypothesis that aortic allograft preincubation in either amino-propanehydroxydiphosphonate (APDP) or AlCl3 would inhibit calcification in a rat subdermal model. Fresh thoracic aortas were harvested under sterile conditions from male Sprague-Dawley rats (350-400 g). APDP aortas were preincubated immediately in either 4 x 10(-3) mol/l, 4 x 10(-4) mol/l, or 4 x 10(-5) mol/l [14C] APDP (37 degrees C, pH 7.4) and controls were incubated in 0.05 mol/l HEPES buffer (pH 7.4, 37 degrees C, 30 min). Al3+ aortas were preincubated in either 10(-1) mol/l, 10(-2) mol/l, or 10(-3) mol/l AlCl3. Pretreated aortas were next implanted subdermally in weanling rats (3-week-old, male, Sprague-Dawley, 50-60 g) and retrieved after 21 days. Control explants retrieved at intervals up to 21 days demonstrated progressive calcification with bulk aortic allograft Ca2+ levels increasing from a preimplant value of 0.8 +/- 0.1 micrograms/mg to 129.8 +/- 12.9 micrograms/mg by 21 days. Light microscopy revealed that much of the calcium deposition was associated with elastin. Calcification was significantly inhibited in the 4 x 10(-3) mol/l and 4 x 10(-4) mol/l APDP preincubated groups was observed (Ca2+ = 0.70 +/- 0.15 micrograms/mg, 36.6 +/- 19.8 micrograms/mg, respectively versus 117.2 +/- 24.3 micrograms/mg, control). Inhibition of calcification in the groups preincubated in the two most concentrated AlCl3 solutions (Ca2+ = 13.9 +/- 4.9 micrograms/mg [10(-2) mol/l AlCl3], 36.6 +/- 7.1 micrograms/mg [10(-3) mol/l AlCl3], 171.0 +/- 13.2 micrograms/mg [control]) was also demonstrated. No adverse effects of either pretreatment, APDP, or AlCl3 were noted on bone or overall somatic growth.

摘要

主动脉同种异体移植管道和瓣膜经常发生钙化性退变。为研究这一问题，建立了无瓣膜主动脉壁同种异体移植皮下钙化的大鼠模型，并开展实验研究以验证以下假说：用氨基丙烷羟基二膦酸盐（APDP）或氯化铝对主动脉同种异体移植物进行预孵育可抑制大鼠皮下模型中的钙化。在无菌条件下从雄性斯普拉格-道利大鼠（350 - 400克）获取新鲜胸主动脉。APDP组主动脉立即分别在4×10⁻³摩尔/升、4×10⁻⁴摩尔/升或4×10⁻⁵摩尔/升的[¹⁴C]APDP中预孵育（37℃，pH 7.4），对照组在0.05摩尔/升HEPES缓冲液（pH 7.4，37℃，30分钟）中孵育。Al³⁺组主动脉分别在10⁻¹摩尔/升、10⁻²摩尔/升或10⁻³摩尔/升的氯化铝中预孵育。接下来，将预处理后的主动脉皮下植入断奶大鼠（3周龄，雄性，斯普拉格-道利，50 - 60克）体内，21天后取出。间隔至21天取出的对照移植物显示出进行性钙化，主动脉同种异体移植物的总钙水平从植入前的0.8±0.1微克/毫克增加到21天时的129.8±12.9微克/毫克。光学显微镜显示，大部分钙沉积与弹性蛋白有关。观察到在4×10⁻³摩尔/升和4×10⁻⁴摩尔/升APDP预孵育组中钙化受到显著抑制（钙含量分别为0.70±0.15微克/毫克、36.6±19.8微克/毫克，而对照组为117.2±24.3微克/毫克）。在两种最高浓度氯化铝溶液预孵育组中也显示出钙化受到抑制（钙含量分别为13.9±4.9微克/毫克[10⁻²摩尔/升氯化铝]、36.6±7.1微克/毫克[10⁻³摩尔/升氯化铝]、171.0±13.2微克/毫克[对照组]）。未观察到APDP或氯化铝预处理对骨骼或总体身体生长有不良影响。