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年龄相关的组织强度和免疫反应损伤在大鼠阴道损伤模型中的作用。

Age-associated impairments in tissue strength and immune response in a rat vaginal injury model.

机构信息

Section of Female Pelvic Medicine & Reconstructive Surgery, Department of Obstetrics & Gynecology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, PO Box 12000, Ein Kerem, Jerusalem, Israel.

Section of Female Pelvic Medicine & Reconstructive Surgery, Departments of Obstetrics & Gynecology and Urology, Medstar-Washington Hospital Center, Georgetown University, Washington, DC, USA.

出版信息

Int Urogynecol J. 2020 Jul;31(7):1435-1441. doi: 10.1007/s00192-019-04008-6. Epub 2019 Jun 26.

DOI:10.1007/s00192-019-04008-6
PMID:31243497
Abstract

INTRODUCTION AND HYPOTHESIS

Surgical repair of pelvic organ prolapse often includes native tissue repair during which the patient's own vaginal connective tissue is used to achieve pelvic support. This method, based on plication and suspension often yields suboptimal anatomical outcomes, possibly due to inadequate healing of the vaginal connective tissue. We hypothesized that age might have a negative effect on the time course and tissue biomechanics of vaginal wound healing in a rat model.

METHODS

Fifty young (12 weeks) and old (12 months) female 344BN Fischer rats were subjected to a posterior midline vaginal incision. The time course of repair was determined by measuring the size of the wound on days 1, 3, 7, and 14 post-injury. These findings correlated with the immune response to injury using a marker of impaired wound healing, the inflammatory cytokine macrophage migration inhibitory factor in the vaginal muscularis. Biomechanical properties of the healed vaginal tissue were tested 30 days post-injury.

RESULTS

Wound healing was assessed on days 1, 3, 7, and 14 post-injury. On day 3 post-injury, the wounds in the young animals had all closed whereas the wounds in the old animals remained open. Furthermore, on day 7, the wound gap was still filled with granulation tissue in the old rats, whereas for the young rats, the wound area was almost indistinguishable from the non-injured area. Macrophage migration inhibitory factor was highly expressed in the vaginal epithelium and in the vaginal muscularis after injury. When compared with young animals, macrophage migration inhibitory factor levels of old rats began to rise more than 2 days later and the increased tissue expression persisted for 7 days longer. The breakpoint force of the healed vagina of old rats was almost 4-fold weaker than in young rats. At 30 days post-injury, the healed vagina in old rats regained less of the original (healthy) force at breakpoint than the young rats.

CONCLUSIONS

In this rat model, age impaired vaginal wound healing, which was reflected in the altered inflammatory response to injury and reduced tissue strength.

摘要

引言与假说

骨盆器官脱垂的外科修复通常包括使用患者自身阴道结缔组织进行的固有组织修复,以实现骨盆支撑。这种基于折叠和悬吊的方法往往产生不理想的解剖结果,可能是由于阴道结缔组织的愈合不足。我们假设年龄可能对阴道伤口愈合的时间过程和组织生物力学产生负面影响。

方法

50 只年轻(12 周)和年老(12 个月)的 344BN 雌性 Fischer 大鼠接受了后中线阴道切开术。通过在受伤后第 1、3、7 和 14 天测量伤口大小来确定修复的时间过程。这些发现与使用受损伤口愈合的标志物,即阴道肌层中的炎症细胞因子巨噬细胞迁移抑制因子,与损伤后的免疫反应相关。在受伤后 30 天测试愈合阴道组织的生物力学特性。

结果

在受伤后第 1、3、7 和 14 天评估伤口愈合。在受伤后第 3 天,年轻动物的伤口均已闭合,而年老动物的伤口仍未闭合。此外,在第 7 天,老年大鼠的伤口间隙仍充满肉芽组织,而年轻大鼠的伤口区域几乎与未受伤区域无法区分。巨噬细胞迁移抑制因子在阴道上皮和阴道肌层受伤后高度表达。与年轻动物相比,老年大鼠的巨噬细胞迁移抑制因子水平升高超过 2 天,并且组织表达增加持续了 7 天以上。老年大鼠愈合阴道的断裂力几乎比年轻大鼠弱 4 倍。在受伤后 30 天,老年大鼠的愈合阴道在断裂点恢复的原始(健康)力比年轻大鼠少。

结论

在这个大鼠模型中,年龄损害了阴道伤口愈合,这反映在对损伤的炎症反应改变和组织强度降低。

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