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在实验性眼外肌手术中评估尼达尼布作为一种新型术后抗瘢痕形成药物的效果。

Evaluation of nintedanib as a new postoperative antiscarring agent in experimental extraocular muscle surgery.

作者信息

Bicaklioglu Gozde, Pirhan Dilara, Yazir Yusufhan, Duruksu Gokhan, Furat Rencber Selenay, Yuksel Nursen

机构信息

Department of Ophthalmology, University of Health Sciences Trabzon Kanuni Training and Research Hospital, Trabzon 61250, Turkey.

Department of Ophthalmology, Kocaeli University, Faculty of Medicine, Kocaeli 41380, Turkey.

出版信息

Int J Ophthalmol. 2022 Jun 18;15(6):914-923. doi: 10.18240/ijo.2022.06.08. eCollection 2022.

Abstract

AIM

To investigate the efficacy of nintedanib on reducing postoperative inflammation, fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide (TA).

METHODS

Reinsertion of superior rectus muscle in right eyes of 30 New Zealand white rabbits were performed. They were randomized to receive one of the following treatments: 0.9% normal saline, one of 1-, 5-, and 10 µmol doses of nintedanib subconjunctivally immediately after surgery and on postoperative day 1, 2, 3, 5, and 7, and TA immediately after surgery. As a control group, unoperated left eyes (=6) were used. On the 28 day, six eyes from each group were enucleated and histopathologically and immunohistochemically analyzed to assess the postoperative inflammatory changes, fibrosis and adhesion. Transforming growth factor beta, matrix metalloproteinase-2 and alpha smooth muscle actin expressions were evaluated.

RESULTS

Conjunctival and scleral inflammation in TA and nintedanib groups were significantly reduced compared to saline (sham) group. Conjunctival vascularity and rectus muscle fibrosis were significantly reduced in 10 µmol nintedanib group. Nintedanib groups were the most effective groups in reduction of perimuscular fibrosis. Neither three nintedanib groups nor TA group differed statistically from sham group with regard to adhesion. The expressions of transforming growth factor beta, alpha smooth muscle actin and matrix metalloproteinase-2 were reduced in nintedanib groups compared to saline group.

CONCLUSION

Nintedanib appears to attenuate postoperative inflammation and fibrosis after extraocular muscle surgery. Nintedanib may be a safer and stronger alternative agent in extraocular muscle surgery when compared to steroids. Further investigation is needed to prove antiadhesive effect of nintedanib.

摘要

目的

与曲安奈德(TA)相比,研究尼达尼布对减少兔眼外肌手术后炎症、纤维化和粘连形成的疗效。

方法

对30只新西兰白兔的右眼进行上直肌重新植入手术。它们被随机分为接受以下治疗之一:0.9%生理盐水、术后立即及术后第1、2、3、5和7天结膜下注射1、5和10 μmol剂量的尼达尼布之一,以及术后立即注射TA。作为对照组,使用未手术的左眼(=6只)。在第28天,每组摘除6只眼,进行组织病理学和免疫组织化学分析,以评估术后炎症变化、纤维化和粘连情况。评估转化生长因子β、基质金属蛋白酶-2和α平滑肌肌动蛋白的表达。

结果

与生理盐水(假手术)组相比,TA组和尼达尼布组的结膜和巩膜炎症明显减轻。10 μmol尼达尼布组的结膜血管化和直肌纤维化明显减轻。尼达尼布组是减少肌周纤维化最有效的组。在粘连方面,三个尼达尼布组和TA组与假手术组相比均无统计学差异。与生理盐水组相比,尼达尼布组中转化生长因子β、α平滑肌肌动蛋白和基质金属蛋白酶-2的表达降低。

结论

尼达尼布似乎可减轻眼外肌手术后的炎症和纤维化。与类固醇相比,尼达尼布在眼外肌手术中可能是一种更安全、更强效的替代药物。需要进一步研究以证实尼达尼布的抗粘连作用。

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本文引用的文献

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Novel Mechanisms for the Antifibrotic Action of Nintedanib.尼达尼布抗纤维化作用的新机制。
Am J Respir Cell Mol Biol. 2016 Jan;54(1):51-9. doi: 10.1165/rcmb.2014-0445OC.
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