Department of Neurosurgery, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey.
Department of Anatomy, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey.
World Neurosurg. 2021 Jun;150:e613-e620. doi: 10.1016/j.wneu.2021.03.065. Epub 2021 Mar 19.
Neural tube defects are among the most frequent congenital abnormalities of the central nervous system. Progression of neural tube deficits is affected by hereditary predilection and environmental determinants. Pethidine (meperidine) is a fast and powerful opioid analgesic in U.S. Food and Drug Administration category C. There are reports about developmental anomalies due to this medication. The aim of this study was to investigate the effects of different doses of pethidine hydrochloride on neural tube development in a chick embryo model resembling the first month of vertebral growth in mammals.
Seventy-five specific pathogen-free eggs were incubated for 28 hours and divided into 5 groups (including the control group), each consisting of 15 eggs. Pethidine hydrochloride was administered sub-blastodermically with a Hamilton microinjector in 4 different doses. Incubation was continued until the end of the 48th hour. Subsequently, all eggs were opened, and embryos were cut from the embryonic membranes and evaluated morphologically, genetically, and histopathologically.
Crown-rump length, somite numbers, and silver-stained nucleolar organizer region (AgNOR) number averages, and total AgNOR/nuclear area ratios decreased in a dose-dependent manner. Examination of neural tube closure revealed statistically significant differences in all experimental groups (P<0.05). Messenger RNA levels of the BRE gene were decreased in pethidine hydrochloride-exposed embryos compared with the control group. Although this downregulation was not statistically significant, this decrease was striking with a 0.422-fold change in the fifth group.
We demonstrated that pethidine hydrochloride affects neuronal development in chicken embryos. The teratogenic mechanism of pethidine hydrochloride is unclear; therefore, further investigation is required.
神经管缺陷是中枢神经系统最常见的先天性畸形之一。神经管缺陷的进展受遗传倾向和环境决定因素的影响。哌替啶（哌替啶）是美国食品和药物管理局 C 类的一种快速而有效的阿片类镇痛药。有报道称这种药物会导致发育异常。本研究旨在研究不同剂量盐酸哌替啶对类似于哺乳动物第 1 个月椎体生长的鸡胚模型中神经管发育的影响。
75 枚无特定病原体鸡蛋孵育 28 小时，分为 5 组（包括对照组），每组 15 枚鸡蛋。盐酸哌替啶用 Hamilton 微量注射器在 4 个不同剂量下进行亚卵裂层给药。孵育持续到第 48 小时结束。随后，所有鸡蛋均被打开，胚胎从胚胎膜中取出，并进行形态学、遗传学和组织病理学评估。
头臀长、体节数和银染核仁组成区（AgNOR）数平均值以及总 AgNOR/核面积比均呈剂量依赖性下降。神经管闭合检查显示所有实验组均有统计学差异（P<0.05）。与对照组相比，暴露于盐酸哌替啶的胚胎中 BRE 基因的信使 RNA 水平降低。尽管这种下调没有统计学意义，但在第 5 组中，这种下降幅度惊人，下降了 0.422 倍。
我们证明了盐酸哌替啶会影响鸡胚的神经元发育。盐酸哌替啶的致畸机制尚不清楚；因此，需要进一步研究。
