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玻璃体内注射贝伐单抗短期治疗后幼年兔视网膜细胞程序性死亡和神经胶质增生减少。

Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after shortterm treatment with intravitreous bevacizumab.

机构信息

Federal University of Rio de Janeiro, Institute of Biophysics, Brazil.

出版信息

Clinics (Sao Paulo). 2012;67(1):61-7. doi: 10.6061/clinics/2012(01)10.

Abstract

OBJECTIVE

Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits.

METHODS

Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test.

RESULTS

No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group.

CONCLUSIONS

Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes.

摘要

目的

贝伐单抗作为血管内皮生长因子拮抗剂,已广泛用于治疗成人视网膜血管增生性疾病,最近也用于治疗早产儿视网膜病变。最近有研究提出,血管内皮生长因子是神经元和神经胶质细胞的保护因子,尤其在发育中的神经组织中。本研究旨在探讨贝伐单抗对幼年兔视网膜发育的影响。

方法

幼年兔一侧眼玻璃体内注射贝伐单抗,另一侧眼作为未治疗对照。治疗前和治疗后 7 天分别进行裂隙灯和眼底检查。同时,采用免疫组织化学方法分析视网膜标本,检测自噬和细胞凋亡以及增殖和神经胶质反应。进行形态计量学分析,并采用曼-惠特尼 U 检验对数据进行分析。

结果

治疗眼和未治疗眼均未观察到临床异常。然而,免疫组织化学分析显示,与未治疗组相比,贝伐单抗治疗组程序性细胞死亡减少,增殖和反应性增加。

结论

贝伐单抗似乎改变了程序性细胞死亡模式,并促进了兔发育中视网膜的神经胶质增生;因此,在发育中的眼睛中应谨慎使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/771b/3248603/788044a0565d/cln-67-01-61-g001.jpg

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