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肾上腺髓质素可改善实验性啮齿动物模型中缺血性左结直肠吻合口的愈合。

Adrenomedulline improves ischemic left colonic anastomotic healing in an experimental rodent model.

机构信息

Department of Surgery, Okmeydani Education and Research Hospital, Okmeydani, Istanbul, Turkey.

出版信息

Clinics (Sao Paulo). 2011;66(10):1805-10. doi: 10.1590/s1807-59322011001000021.

Abstract

BACKGROUND

Leakage from colonic anastomosis is a major complication causing increased mortality and morbidity. Ischemia is a well-known cause of this event. This study was designed to investigate the effects of adrenomedullin on the healing of ischemic colon anastomosis in a rat model.

METHODS

Standardized left colon resection 3 cm above the peritoneal reflection and colonic anastomosis were performed in 40 Wistar rats that were divided into four groups. To mimic ischemia, the mesocolon was ligated 2 cm from either side of the anastomosis in all of the groups. The control groups (1 and 2) received no further treatment. The experimental groups (3 and 4) received adrenomedullin treatment. Adrenomedullin therapy was started in the perioperative period in group 3 and 4 rats (the therapeutic groups). Group 1 and group 3 rats were sacrificed on postoperative day 3. Group 2 and group 4 rats were sacrificed on postoperative day 7. After careful relaparotomy, bursting pressure, hydroxyproline, malondialdehyde, interleukin 6, nitric oxide, vascular endothelial growth factor, and tumor necrosis factor alpha levels were measured. Histopathological characteristics of the anastomosis were analyzed.

RESULTS

The group 3 animals had a significantly higher bursting pressure than group 1 (p<0.05). Hydroxyproline levels in group 1 were significantly lower than in group 3 (p<0.05). The mean bursting pressure was significantly different between group 2 and group 4 (p<0.05). Hydroxyproline levels in groups 3 and 4 were significantly increased by adrenomedullin therapy relative to the control groups (p<0.05). When all groups were compared, malondialdehyde and nitric oxide were significantly lower in the control groups (p<0.05). When vascular endothelial growth factor levels were compared, no statistically significant difference between groups was observed. Interleukin 6 and tumor necrosis factor alpha were significantly decreased by adrenomedullin therapy (p<0.05). The healing parameters and inflammatory changes (e.g., granulocytic cell infiltration, necrosis, and exudate) were significantly different among all groups (p<0.05).

CONCLUSION

Adrenomedullin had positive effects on histopathologic anastomotic healing in this experimental model of ischemic colon anastomosis.

摘要

背景

结肠吻合口漏是导致死亡率和发病率增加的主要并发症。缺血是导致这种情况的一个已知原因。本研究旨在探讨肾上腺髓质素对大鼠模型缺血性结肠吻合口愈合的影响。

方法

在 40 只 Wistar 大鼠中进行标准的左结肠切除,切除位置在腹膜反射上方 3cm 处,并进行结肠吻合术。为了模拟缺血,所有组别的横结肠系膜均在吻合口两侧 2cm 处结扎。对照组(1 组和 2 组)未进行进一步治疗。实验组(3 组和 4 组)接受肾上腺髓质素治疗。在 3 组和 4 组大鼠(治疗组)的围手术期开始进行肾上腺髓质素治疗。第 1 组和第 3 组大鼠于术后第 3 天处死。第 2 组和第 4 组大鼠于术后第 7 天处死。仔细剖腹后,测量爆裂压、羟脯氨酸、丙二醛、白细胞介素 6、一氧化氮、血管内皮生长因子和肿瘤坏死因子-α水平,并分析吻合口的组织病理学特征。

结果

第 3 组动物的爆裂压显著高于第 1 组(p<0.05)。第 1 组的羟脯氨酸水平明显低于第 3 组(p<0.05)。第 2 组和第 4 组的平均爆裂压差异有统计学意义(p<0.05)。与对照组相比,肾上腺髓质素治疗组 3 和 4 的羟脯氨酸水平显著升高(p<0.05)。当所有组进行比较时,对照组的丙二醛和一氧化氮明显较低(p<0.05)。当比较血管内皮生长因子水平时,各组之间无统计学差异。肾上腺髓质素治疗显著降低白细胞介素 6 和肿瘤坏死因子-α(p<0.05)。所有组之间的愈合参数和炎症变化(如粒细胞浸润、坏死和渗出)均有显著差异(p<0.05)。

结论

在本缺血性结肠吻合术实验模型中,肾上腺髓质素对组织病理学吻合口愈合有积极影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c125/3181232/eac3520a1680/cln-66-10-1805-g001.jpg

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