Alpha-1-antitrypsin improves anastomotic healing in intestinal epithelial cells model.

IF 1.5 3区医学 Q2 PEDIATRICS Pediatric Surgery International Pub Date : 2024-09-30 DOI:10.1007/s00383-024-05841-7

Nagoud Schukfeh, Kokilavani Sivaraman, Aileen Schmidt, Gertrud Vieten, Jens Dingemann, Johannes Weidner, Ruth Olmer, Sabina Janciauskiene

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Abstract

Purpose: Intestinal anastomosis is a routine procedure in pediatric surgery, with leakage being a significant complication. Human alpha1-antitrypsin (AAT), whose physiological serum concentrations range from 0.9-2.0 mg/ml, is known to accelerate wound healing and stimulate the expression of cell proliferation-related genes. We hypothesized that AAT might enhance anastomotic healing.

Methods: In a monolayer of non-tumorigenic HIEC-6 epithelial cells derived from fetal intestine a scratch was created. Standard medium without (control) or with AAT (0.5 and 1 mg/ml) was added. Cells were observed using a Life-Cell Imaging System. Cell proliferation was assessed, and the expression of proliferation-related genes was measured by qRT-PCR.

Results: In the presence of AAT, the scratch closed significantly faster. Cells treated with 1 mg/ml AAT showed 53% repopulation after 8 h and 97% after 18 h, while control cells showed 24% and 60% repopulation, respectively (p < 0.02). The treatment with AAT induced HIEC-6-cell proliferation and significantly increased the mRNA-expression of CDKN1A, CDKN2A, ANGPTL4, WNT3 and COL3A1 genes. AAT did not change the mRNA-expression of CXCL8 but decreased levels of IL-8 as compared to controls.

Conclusion: At physiological concentrations AAT accelerates the confluence of intestinal cells and increases cell proliferation. The local administration of AAT may bear therapeutic potential to improve anastomotic healing.

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α-1-抗胰蛋白酶可改善肠上皮细胞模型中吻合口的愈合。

目的：肠吻合术是小儿外科的常规手术，渗漏是一个重要的并发症。人α1-抗胰蛋白酶（AAT）的生理血清浓度为 0.9-2.0 毫克/毫升，已知它能加速伤口愈合并刺激细胞增殖相关基因的表达。我们假设 AAT 可促进吻合口愈合：方法：在取自胎儿肠道的非肿瘤性 HIEC-6 上皮细胞单层中制造划痕。加入不含（对照组）或含 AAT（0.5 和 1 毫克/毫升）的标准培养基。使用 Life-Cell 成像系统观察细胞。评估细胞增殖，并通过 qRT-PCR 测定增殖相关基因的表达：结果：在有 AAT 存在的情况下，划痕闭合的速度明显加快。用 1 mg/ml AAT 处理的细胞在 8 小时后有 53% 的细胞再增殖，18 小时后有 97% 的细胞再增殖，而对照组细胞分别有 24% 和 60% 的细胞再增殖（p < 0.02）。AAT 可诱导 HIEC-6 细胞增殖，并显著增加 CDKN1A、CDKN2A、ANGPTL4、WNT3 和 COL3A1 基因的 mRNA 表达。与对照组相比，AAT 没有改变 CXCL8 的 mRNA 表达，但降低了 IL-8 的水平：结论：在生理浓度下，AAT 可加速肠细胞的汇合并增加细胞增殖。结论：在生理浓度下，AAT 可加速肠道细胞的汇合并增加细胞增殖，局部给药 AAT 可能具有改善吻合口愈合的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Surgery International 医学-外科

CiteScore

3.00

自引率

5.60%

发文量

215

审稿时长

3-6 weeks

期刊介绍： Pediatric Surgery International is a journal devoted to the publication of new and important information from the entire spectrum of pediatric surgery. The major purpose of the journal is to promote postgraduate training and further education in the surgery of infants and children. The contents will include articles in clinical and experimental surgery, as well as related fields. One section of each issue is devoted to a special topic, with invited contributions from recognized authorities. Other sections will include: -Review articles- Original articles- Technical innovations- Letters to the editor