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宫内暴露于奥卡西平和加巴喷丁对出生后时期脑组织凋亡作用的流式细胞术检测。

Flow cytometric examination of apoptotic effect on brain tissue in postnatal period created by intrauterine oxcarbazepine and gabapentin exposure.

作者信息

Erisgin Z, Tekelioglu Y

出版信息

Bratisl Lek Listy. 2017;118(2):107-111. doi: 10.4149/BLL_2017_022.

Abstract

OBJECTIVE

For epileptics, pregnancy contains the balance between no seizure period and antiepileptic use having the least teratogenicity risk. The purpose is to analyse with flow cytometry the apoptotic effects on postnatal brain tissue caused by prenatal use of second generation antiepileptics oxcarbazepine (OXC) and gabapentin (GBP) having different effect mechanisms.

METHOD

30 (n = 5 each group) Wistar albino male rats (45-days-old) are used. First 3 groups are exposed to OXC (100 mg/kg/day), GBP (50 mg/kg/day), and saline, respectively on the 1st-5th prenatal days (preimplantation-implantation period) while the second 3 groups are exposed to the same substances on the 6th-15th prenatal days (organogenesis), respectively. After sacrifice, brain tissue samples were made into suspension with mechanic and enzymatic digestion and examined with flow cytometry.

RESULTS

While apoptosis rate appeared high in rats exposed to OXC on the 1st-5th (p < 0.001) and 6th-15th days (p < 0.001), no significant difference occurred for GBP (p = 0.004; p = 0.012) and saline (p = 0.012). Considering time effect in three treatment groups, while difference was not significant for PSS and GBP groups (p = 0.847 and p = 0.934), apoptosis rate was significantly high for OXC on the 6th-15th days compared to the 1st-5th days (p < 0.001).

CONCLUSION

It is observed that the use of OXC causes neurotoxicity during preimplantation, implantation and, especially, organogenesis period (neurogenesis) whereas GBP does not (Fig. 3, Ref. 32).

摘要

目的

对于癫痫患者而言,孕期需要在无癫痫发作期与使用致畸风险最小的抗癫痫药物之间保持平衡。本研究旨在通过流式细胞术分析产前使用具有不同作用机制的第二代抗癫痫药物奥卡西平(OXC)和加巴喷丁(GBP)对产后脑组织的凋亡影响。

方法

选用30只(每组n = 5)45日龄的Wistar白化雄性大鼠。前3组在产前第1 - 5天(着床前期 - 着床期)分别暴露于奥卡西平(100 mg/kg/天)、加巴喷丁(50 mg/kg/天)和生理盐水,而后3组在产前第6 - 15天(器官形成期)分别暴露于相同物质。处死后,通过机械和酶消化将脑组织样本制成悬液,并用流式细胞术进行检测。

结果

在第1 - 5天(p < 0.001)和第6 - 15天(p < 0.001)暴露于奥卡西平的大鼠中,凋亡率较高,而加巴喷丁组(p = 0.004;p = 0.012)和生理盐水组(p = 0.012)未出现显著差异。考虑三个治疗组的时间效应,虽然PSS组和加巴喷丁组差异不显著(p = 0.847和p = 0.934),但与第1 - 5天相比,奥卡西平在第6 - 15天的凋亡率显著升高(p < 0.001)。

结论

研究观察到,奥卡西平的使用在着床前期、着床期尤其是器官形成期(神经发生期)会导致神经毒性,而加巴喷丁则不会(图3,参考文献32)。

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