张瑞萍1,
王珂1,
魏琳颜1,
赵粉线1,
薛红丽1,
李芝兰1
1. 兰州大学公共卫生学院, 兰州 730000;
2. 宝鸡市疾病预防控制中心, 宝鸡 721006
作者简介: 罗波艳(1989-),女,硕士研究生,研究方向为生殖毒理学,E-mail:luoby14@lzu.edu.cn.
基金项目: 中央高校基本科研业务费专项基金项目(lzujbky-2016-24)中图分类号: X171.5
The Effects of Acrylonitrile-Exposure on Brain Tissue and the Key Protein Expression of iNOS/p38 MAPK Signaling Pathway in Rats
Luo Boyan1,2,Zhang Ruiping1,
Wang Ke1,
Wei Linyan1,
Zhao Fenxian1,
Xue Hongli1,
Li Zhilan1
1. School of Public Health, Lanzhou University, Lanzhou 730000, China;
2. Baoji Center for Desease Control and Prevention, Baoji 721006, China
CLC number: X171.5
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摘要:通过探究iNOS/p38 MAPK信号通路在丙烯腈(acrylonitrile，ACN)诱导脑组织损伤中的作用，为进一步研究ACN的神经毒性作用提供依据。选取50只SPF级健康成年雄性SD大鼠，随机分为5组，每组10只。适应性饲养一周后，以12.5、25.0、50.0 mg·kg-1 ACN对大鼠进行灌胃染毒，对照组给予玉米油，另设NAC组(300.0 mg·kg-1 NAC+ 50.0 mg·kg-1 ACN)，1次·天-1，6天·周-1，共染毒13周。次日称重并处死大鼠，测定大鼠脑组织NO含量、总NOS水平及iNOS、p-p38和p38蛋白表达水平。结果显示，ACN各剂量组大鼠脑组织脏器系数与对照组比较均显著降低(P<0.05)，高剂量组大鼠脑脏器系数与NAC组比较降低(P>0.05)。高剂量组NO含量和总NOS水平显著高于对照组，与NAC组比较，高剂量组NO含量降低(P>0.05)，总NOS水平升高(P>0.05)。Western blot结果显示，ACN高剂量组大鼠脑组织iNOS、p-p38蛋白表达水平和p-p38/p38比值显著高于对照组和NAC组(P<0.05)。ACN可激活iNOS/p38MAPK信号通路，这可能是ACN致大鼠脑组织损伤的机制之一。
关键词: 丙烯腈/
大鼠/
iNOS/
p38 MAPK
Abstract:To investigate the effects of iNOS/p38 MAPK signaling pathway induced via acrylonitrile (ACN) on brain injury, which are beneficial to provide the basis for neurological toxicity of ACN, we randomly distributed fifty healthy adult male SD rats into five groups of 10 rats each. After adaptive feeding for one week, rats in the exposed groups were respectively treated with doses of 12.5, 25.0 and 50.0 mg·kg-1 of ACN via gavage, and the control group was given corn oil. After being treated with 50.0 mg·kg-1 ACN 30 minutes, rats in the N-acetylcysteine (NAC) group were treated with 300.0 mg·kg-1 NAC. All the rats were gavaged once a day, six days per week. The final body weights were recorded after 13 weeks, then all rats were sacrificed. The contents of nitric oxide (NO) and the activities of total nitric oxide synthase (tNOS) in rats brains were detected. The expression levels of inducible or immunological nitric oxide synthase (iNOS), phospho-p38 and p38 proteins were also measured by Western blot. Results showed that the relative organ weights of the rat brain tissues in the low, medium and high dose groups were significantly lower than that in the control group, but no significant difference between NAC group and the high dose group. Compared with the control group, marked increase of NO level and the activities of tNOS in the high group were observed. However, there was no significant difference in the level of NO and the activities of tNOS between NAC group and the high dose group. And the levels of iNOS, phospho-p38 proteins and the ratios of phospho-p38 protein to p38 protein in the high dose group were significantly higher than that in the control and NAC group. The activation of iNOS/p38 MAPK signaling pathway may be one of the mechanisms of brain injury induced by ACN in rats.
Key words:acrylonitrile/
rats/
iNOS/
p38 MAPK.
