Surgical Department, University Hospital of the RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
Langenbecks Arch Surg. 2010 Apr;395(4):429-35. doi: 10.1007/s00423-009-0473-0. Epub 2009 Mar 7.
Adrenal hormones influence inflammatory and fibrotic activity and thereby are involved in wound-healing process. Any excess as well as any shortage of glucocorticoids leads to a delayed wound healing. Mineralocorticoids like aldosterone have a pro-fibrotic and pro-inflammatory impact; thus, reduction of circulating aldosterone should result in an attenuated inflammatory response to implanted foreign bodies.
Eighteen rats were bilaterally adrenalectomized and substituted with dexamethasone (12 microg/kg per day) and 1% salt in their drinking water; 22 rats were sham-operated. The surgical suture material was removed after 3 weeks and analyzed for size of granuloma, ratio of collagen type I/III, apoptotic cells (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling), expression of matrix metalloproteinase (MMP)-2, cyclooxygenase 2, tumor necrosis factor receptor 2 (TNF-R2), cluster of differentiation 68 (CD68), Ki67, and cold shock protein Y box binding protein 1 (YB-1). Cell expression was scored according to Remmele.
All animals developed foreign body granulomas around the sutures. Absence of circulating aldosterone after adrenalectomy (ADX) was associated with smaller granuloma size and a reduced ratio of collagen type I/III. Ki67 and MMP-2 showed the strongest expression in cells of the infiltrate around suture. In adrenalectomized rats, we observed significantly less CD68-positive macrophages and less Ki67-positive cells but no significant differences in the expression of YB-1, TNF-R2, or MMP-2. Looking for correlations and co-expressions of proteins, the number of significant Spearman correlations was reduced in the ADX group compared to controls (one and four, respectively).
The absence of circulating aldosterone attenuates inflammatory intensity around suture material. Foreign body granuloma seems to be an appropriate model to study chronic inflammatory process.
肾上腺激素影响炎症和纤维化活动,从而参与伤口愈合过程。糖皮质激素过多或不足都会导致伤口愈合延迟。醛固酮等盐皮质激素具有促纤维化和促炎作用;因此,降低循环醛固酮水平应会导致植入异物的炎症反应减弱。
18 只大鼠双侧肾上腺切除术,并用地塞米松(每天 12μg/kg)和 1%盐替代饮用水;22 只大鼠假手术。3 周后取出手术缝线材料,分析肉芽肿大小、I 型/III 型胶原比、凋亡细胞(末端脱氧核苷酸转移酶脱氧尿苷三磷酸末端标记)、基质金属蛋白酶(MMP)-2、环氧化酶 2、肿瘤坏死因子受体 2(TNF-R2)、分化群 68(CD68)、Ki67 和冷休克蛋白 Y 框结合蛋白 1(YB-1)的表达。根据 Remmele 对细胞表达进行评分。
所有动物缝线周围均形成异物肉芽肿。肾上腺切除术(ADX)后循环醛固酮缺乏与肉芽肿体积减小和 I 型/III 型胶原比降低有关。Ki67 和 MMP-2 在缝线周围浸润细胞中的表达最强。在肾上腺切除大鼠中,我们观察到 CD68 阳性巨噬细胞和 Ki67 阳性细胞明显减少,但 YB-1、TNF-R2 或 MMP-2 的表达没有差异。寻找蛋白质的相关性和共表达,与对照组相比,ADX 组的显著 Spearman 相关性数量减少(分别为 1 和 4)。
循环醛固酮缺乏可减轻缝线周围的炎症强度。异物肉芽肿似乎是研究慢性炎症过程的合适模型。