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玻璃体内注射贝伐单抗在孕鼠模型中的致畸作用

Teratogenic Effects of Intravitreal Injection of Bevacizumab in a Pregnant Rat Model.

作者信息

Bamdad Shahram, Bamdad Mina, Khanlari Mahsa, Daneshbod Yahya, Khademi Behzad

机构信息

Department of ophthalmology, Shiraz University of Medical Sciences (SUMS), Shiraz, Iran.

Department of Developmental Biology, Islamic Azad University, Shiraz, Iran.

出版信息

Iran J Pharm Res. 2017 Spring;16(2):670-676.

Abstract

In this research study, to investigate teratogenic effect of intravitreal injection of bevacizumab in pregnant rat model, twenty seven female Wistar rats were inseminated. Pregnant rats were divided into 6 groups (three groups as case and three as control groups). Each case and control groups were divided according to the day of intravitreal injections (day 2, 10 and 18). Rats in the case groups received 4 µL intravitreal injection of bevacizumab and the control groups received the same volume of distilled water. The tail and umbilical cord length in case groups 1, 2, and 3 did not display any significant differences compared to their control groups. The fetal weight was significantly lower in the case groups 1 (p>0.001) and 2 (p>0.001) compared to their control groups. Furthermore, the placental weight was only lower in the case group 1 (p>0.001). Case group 2 had a shorter crown rump length in comparison with its control group (p=0.029). Morphological investigations showed two abnormal cases of gastroschisis in group 1 and a case of a cleft in the skull in one of the rats in case group 2. The results show that intravitreal bevacizumab has developmental effect when administered in the early stages of pregnancy; but it is safe when administered in the last week of pregnancy in rats.

摘要

在本研究中,为了探究玻璃体内注射贝伐单抗在孕鼠模型中的致畸作用,对27只雌性Wistar大鼠进行了授精。将孕鼠分为6组(3组为病例组,3组为对照组)。每个病例组和对照组根据玻璃体内注射的日期(第2天、第10天和第18天)进行划分。病例组大鼠接受4µL玻璃体内贝伐单抗注射,对照组接受相同体积的蒸馏水。病例组1、2和3的尾巴和脐带长度与各自对照组相比未显示出任何显著差异。病例组1(p>0.001)和2(p>0.001)的胎儿体重明显低于各自对照组。此外,仅病例组1的胎盘重量较低(p>0.001)。病例组2的顶臀长度与其对照组相比更短(p=0.029)。形态学研究显示,病例组1中有2例腹裂异常病例,病例组2中的1只大鼠出现颅骨裂病例。结果表明,玻璃体内注射贝伐单抗在妊娠早期给药时有发育影响;但在大鼠妊娠最后一周给药时是安全的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afea/5603876/4355ea618b59/ijpr-16-670-g001.jpg

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