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局部莫特塞尼布对实验性角膜新生血管模型的影响。

Effect of topical motesanib in experimental corneal neovascularization model.

机构信息

Department of Ophthalmology, Faculty of Medicine, Fırat University, 23119, Elazığ, Turkey.

Department of Ophthalmology, Elazig Fethi Sekin City Hospital, 23119, Elazığ, Turkey.

出版信息

Int Ophthalmol. 2023 Aug;43(8):2989-2997. doi: 10.1007/s10792-023-02685-3. Epub 2023 Mar 27.

Abstract

PURPOSE

This study aimed to compare the efficacy of topical bevacizumab and motesanib in an experimental corneal neovascularization model, and find the most effective motesanib dose.

MATERIALS AND METHODS

In experiments, 42 Wistar Albino rats were randomly divided into six groups (n = 7). Corneal cauterization was applied to all groups except the group 1. Group 1 did not receive any treatment. Topical dimethylsulfoxide was applied to sham group three times a day(tid). Topical bevacizumab drops (5 mg/ml) were applied to Group 3 tid. Topical motesanib drops with a dose of 2.5, 5, and 7.5 mg/ml were respectively applied in Groups 4, 5, and 6 tid. On the 8th day, corneal photographs of all rats were taken under general anesthesia, and the percentage of corneal neovascular area was calculated. VEGF-A mRNA, VEGFR-2 mRNA, miRNA-21, miRNA-27a, miRNA-31, miRNA-126, miRNA-184, and miRNA-204 were evaluated by the qRT-PCR method in corneas taken after decapitation.

RESULTS

The percentage of corneal neovascularization areas and VEGF-A mRNA expression levels were decreased in all treatment groups compared to group 2 (p < 0.05). VEGFR-2 mRNA levels were found to be statistically significantly decreased in groups 4 and 6 compared to group 2 (p < 0.05). Statistically significant changes were detected in the expression levels of only miRNA-126 among all miRNAs.

CONCLUSION

Motesanib with a dose of 7.5 mg/ml statistically significantly suppressed the VEGFR-2 mRNA level compared with other treatment doses and may be more effective than bevacizumab. Further, miRNA-126 can be used as a proangiogenic marker.

摘要

目的

本研究旨在比较贝伐单抗和莫特塞尼布在实验性角膜新生血管模型中的疗效,并确定最有效的莫特塞尼布剂量。

材料和方法

在实验中,将 42 只 Wistar 白化大鼠随机分为六组(n = 7)。除第 1 组外,所有组均进行角膜烧灼。第 1 组未接受任何治疗。第 3 组每天接受 3 次眼部涂抹二甲基亚砜(tid)。第 3 组每天接受 3 次眼部滴注 5mg/ml 的贝伐单抗。第 4、5、6 组分别接受 2.5、5 和 7.5mg/ml 的莫特塞尼布滴眼治疗 tid。所有大鼠在全身麻醉下于第 8 天拍摄角膜照片,计算角膜新生血管面积百分比。通过 qRT-PCR 方法评估取下头颅后的角膜中 VEGF-A mRNA、VEGFR-2 mRNA、miRNA-21、miRNA-27a、miRNA-31、miRNA-126、miRNA-184 和 miRNA-204 的表达水平。

结果

与第 2 组相比,所有治疗组的角膜新生血管面积百分比和 VEGF-A mRNA 表达水平均降低(p < 0.05)。与第 2 组相比,第 4 和第 6 组的 VEGFR-2 mRNA 水平明显降低(p < 0.05)。在所有 miRNA 中,仅 miRNA-126 的表达水平有统计学显著变化。

结论

与其他治疗剂量相比,莫特塞尼布 7.5mg/ml 剂量可显著抑制 VEGFR-2 mRNA 水平,可能比贝伐单抗更有效。此外,miRNA-126 可作为促血管生成的标志物。

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