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双硫仑在实验性大鼠子宫角模型中预防术后粘连形成的效果。

The Effect of Disulfiram in the Prevention of Postoperative Adhesion Formation in an Experimental Rat Uterine Horn Model.

机构信息

Department of Obstetrics and Gynecology, Etlik Zübeyde Hanım Women's Health Training and Research Hospital, 06010, Ankara, Turkey.

Department of Obstetrics and Gynecology, Bahceci Health Group, Istanbul, Turkey.

出版信息

Reprod Sci. 2021 Sep;28(9):2650-2660. doi: 10.1007/s43032-021-00543-0. Epub 2021 Mar 29.

Abstract

Postoperative adhesions can cause serious complications, including intestinal obstruction, chronic abdominopelvic pain, and infertility in women. Here we investigate the effects of disulfiram on the postoperative adhesion model. Female Wistar rats were used (n = 72). The animals were separated into six groups (12 rats per group): group 1 (control), group 2 (300 mg/kg disulfiram administered for 3 days preoperatively), group 3 (50 mg/kg disulfiram administered for 3 days preoperatively and 14 days postoperatively), group 4 (300 mg/kg disulfiram administered for 3 days preoperatively and 14 days postoperatively), group 5 (50 mg/kg disulfiram administered 14 days postoperatively only), and group 6 (300 mg/kg disulfiram administered 14 days postoperatively only). A histopathologic examination was performed. Immunohistochemical stainings for matrix metalloproteinase-2 and 9 (MMP-2, and MMP-9) and vascular endothelial growth factor (VEGF) were evaluated. The macroscopic adhesion scores were significantly lower in the disulfiram groups (groups 3, 4, and 6) compared to the control group (p < 0.05). Inflammation scores were lower in all groups receiving disulfiram, but only reached statistical significance in group 4 (p < 0.05). In the immunohistochemical evaluation of the groups, MMP-9 was significantly lower in group 5 than group 4 (p < 0.05). There was no significant difference between the groups for MMP-2 and VEGF. We found that disulfiram reduced postoperative adhesion formation. Disulfiram becomes more effective (by directly reducing inflammation) when initiated during the preoperative period at high doses.

摘要

术后粘连可导致严重并发症,包括肠梗阻、慢性腹盆腔疼痛和女性不孕。在此,我们研究了双硫仑对术后粘连模型的影响。使用雌性 Wistar 大鼠(n = 72)。将动物分为六组(每组 12 只大鼠):第 1 组(对照组)、第 2 组(术前 3 天给予 300mg/kg 双硫仑)、第 3 组(术前 3 天和术后 14 天给予 50mg/kg 双硫仑)、第 4 组(术前 3 天和术后 14 天给予 300mg/kg 双硫仑)、第 5 组(仅术后 14 天给予 50mg/kg 双硫仑)和第 6 组(仅术后 14 天给予 300mg/kg 双硫仑)。进行组织病理学检查。评估基质金属蛋白酶-2 和 9(MMP-2 和 MMP-9)和血管内皮生长因子(VEGF)的免疫组织化学染色。与对照组相比,双硫仑组(第 3、4 和 6 组)的宏观粘连评分显著降低(p < 0.05)。所有接受双硫仑治疗的组的炎症评分均较低,但仅在第 4 组达到统计学意义(p < 0.05)。在组的免疫组化评价中,第 5 组的 MMP-9 明显低于第 4 组(p < 0.05)。MMP-2 和 VEGF 各组之间无显著差异。我们发现双硫仑可减少术后粘连形成。当在术前期间以高剂量开始时,双硫仑(通过直接减少炎症)变得更有效。

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