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[苯并(a)芘对大鼠脑组织神经元细胞凋亡及Bcl-2和Bax蛋白表达的影响]

[Effects of benzo(a)pyrene on apoptosis of neuronal cells and expression of Bcl-2 and Bax proteins in rat brain tissue].

作者信息

Zhao Jie, Wang Lin-ping, Nie Ji-sheng, Niu Qiao

机构信息

Center for Disease Control and Prevention of Shanxi Tai Gang, Taiyuan 030003, China.

出版信息

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2011 Nov;29(11):820-4.

Abstract

OBJECTIVE

To observe the effects of Benzo(a)pyrene (BaP) on apoptosis of neuronal cells and expression of Bcl-2 and Bax proteins and to explore the mechanism of neurotoxicity induced by BaP in rats.

METHODS

A total of 32 SD rats were divided randomly into 4 groups, i.e. 3 BaP (126.2, 63.1 and 31.5 µg/kg) groups and a solvent control (50 µg/kg olive oil) group. All rats were exposed to BaP or olive oil by lateral cerebral ventricle micro-injection 1 time a week for 3 weeks. The apoptosis of neuronal cells was detected with TdT-mediated dUTP-biotin nicked labeling (TUNEL) assay and the expression levels of Bcl-2 and Bax were measured with SABC immunohistochemistry in the cerebral cortex and hippocampus tissues of rats.

RESULTS

The results of TUNEL assay showed that apoptosis bodies on the surface of the neurons in the cerebral cortex and hippocampus were clearly observed and the number of apoptosis bodies increased with BaP. Apoptosis indexes (AIs) of the rat cerebral cortex and hippocampus in high exposure group were significantly higher than those in control group (P < 0.05 or P < 0.01). The analysis of immunohistochemistry showed that the Bcl-2 expression levels significantly decreased, the Bax expression levels obviously increased and the ratio of Bcl-2 to Bax decreased in the rat cerebral cortex and hippocampus of medium and high exposure groups, as compared with control group (P < 0.05 or P < 0.01). In the rat cerebral cortex and hippocampus, there were the negative correlation (r = -0.927, P < 0.01; r = -0.934, P < 0.01) between AI and Bcl-2, the positive correlation (r = 0.858, P < 0.01; r = 0.847, P < 0.01) between AI and Bax and the negative correlation (r = -0.939, P < 0.01; r = -0.942, P < 0.01) between AI and Bcl-2/Bax.

CONCLUSION

BaP could induce the apoptosis of neuronal cells in the rat cerebral cortex and hippocampus. Bcl-2 and Bax protein expression may play an important role in the apoptosis of neuronal cells induced by BaP.

摘要

目的

观察苯并(a)芘(BaP)对神经元细胞凋亡及Bcl-2和Bax蛋白表达的影响,探讨BaP诱导大鼠神经毒性的机制。

方法

将32只SD大鼠随机分为4组,即3个BaP(126.2、63.1和31.5 μg/kg)组和1个溶剂对照组(50 μg/kg橄榄油)。所有大鼠每周经侧脑室微量注射1次BaP或橄榄油,共3周。采用TdT介导的dUTP生物素缺口末端标记法(TUNEL法)检测神经元细胞凋亡,用SABC免疫组织化学法检测大鼠大脑皮质和海马组织中Bcl-2和Bax的表达水平。

结果

TUNEL法结果显示,大脑皮质和海马神经元表面可见明显的凋亡小体,且凋亡小体数量随BaP剂量增加而增多。高剂量染毒组大鼠大脑皮质和海马的凋亡指数(AI)显著高于对照组(P < 0.05或P < 0.01)。免疫组织化学分析显示,中、高剂量染毒组大鼠大脑皮质和海马中Bcl-2表达水平显著降低,Bax表达水平明显升高,Bcl-2与Bax的比值降低,与对照组相比差异有统计学意义(P < 0.05或P < 0.01)。在大鼠大脑皮质和海马中,AI与Bcl-2呈负相关(r = -0.927,P < 0.01;r = -0.934,P < 0.01),AI与Bax呈正相关(r = 0.858,P < 0.01;r = 0.847,P < 0.01),AI与Bcl-2/Bax呈负相关(r = -0.939,P < 0.01;r = -0.942,P < 0.01)。

结论

BaP可诱导大鼠大脑皮质和海马神经元细胞凋亡。Bcl-2和Bax蛋白表达可能在BaP诱导的神经元细胞凋亡中起重要作用。

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