抗癫痫药丙戊酸钠对大鼠正常脑组织的放射保护作用

doi:10.6040/j.issn.1671-7554.0.2015.230

摘要/Abstract

摘要： 目的探讨丙戊酸钠(VPA)对大鼠正常脑组织的放射保护作用。方法 48只雄性Wistar大鼠随机分为VPA组、放疗组、联合组和对照组,每组12只。VPA组给予假照射和VPA注射(150 mg/kg,2次/d,共5 d);放疗组给予X线照射和生理盐水注射(150 mg/kg,2次/d,共5 d);联合组给予X线照射和VPA注射(150 mg/kg,2次/d,共5 d);对照组给予假照射和生理盐水注射(150 mg/kg,2次/d,共5 d)。放疗后24 h,采用免疫组化法检测脑组织Caspase-3的表达观察细胞凋亡。记录大鼠自VPA注射后2周内体质量变化。放疗后6个月,电镜观察脑组织神经元细胞核的改变。结果免疫组化结果显示,放疗组与联合组相比可见明显Caspase-3表达。放疗组平均体质量明显低于其他各组,与联合组相比,体质量明显下降(P<0.05)。电镜结果显示,放疗组神经元核膜表面凹凸不平,不规整,甚至有损伤;联合组神经元核膜表面轻度不规整、没有损伤;对照组和VPA组神经元未见异常表现。结论 VPA对正常脑组织具有放射保护作用,其机制与抑制X线诱导的正常细胞凋亡有关。

关键词: 分割放疗, 细胞凋亡, 组蛋白去乙酰化酶抑制剂, 丙戊酸钠, 放射保护

Abstract: Objective To investigate the radioprotective effects of valproic acid (VPA), an antiepileptic drug, on the normal brain tissues of rats. Methods A total of 48 male Wistar rats were randomized into VPA group, radiotherapy group, combined group, control group, with 12 animals in each group. VPA group received sham irradiation plus VPA 150 mg/kg; radiotherapy group underwent X-ray irradiation plus physiological saline 150 mg/kg; combined group received X-ray irradiation plus VPA 150 mg/kg; control group received sham irradiation plus physiological saline 150 mg/kg. All treatments were administered twice a day for 5 days. Cell apoptosis of the brain tissues was determined with immunohistochemistry using an antibody for protein Caspase-3 24 hours after irradiation. Then the changes of body weight within 2 weeks starting from the first injection of VPA were recorded. The neuron nucleus changes were observed with transmission electron microscope (TEM) 6 months after radiotherapy. Results Immunohistochemistry results demonstrated that Caspase-3 was significantly increased in radiotherapy groups compared to the combined group. The average weight of rats in radiotherapy group decreased markedly compared with the combined group (P<0.05). TEM observation showed that neuron nuclear membrane surface was conveoconcave and irregular, or even impaired in radiotherapy group; it was a little conveoconcave in combined group, but no impairment was observed; no apparent abnormalities were observed in control group and VPA group. Conclusion VPA could protect normal brain tissues of rats by inhibiting the apoptosis of normal nerve cells arising from radiation.

Key words: Histone deacetylase inhibitors, Valproic acid, Radioprotection, Apoptosis, Fractionated radiotherapy

中图分类号:

R815.2

张伟, 周勇, 牛俊婕, 徐英, 侯华英, 姜玉华. 抗癫痫药丙戊酸钠对大鼠正常脑组织的放射保护作用[J]. 山东大学学报（医学版）, 2015, 53(10): 11-15.

ZHANG Wei, ZHOU Yong, NIU Junjie, XU Ying, HOU Huaying, JIANG Yuhua. Radioprotective effects of valproic acid on normal brain tissues of rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(10): 11-15.

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