甲苯对大鼠中枢神经系统的亚慢性毒作用

Sub-chronic Toxicity of Toluene on the Central Nervous System of Rats

  • 摘要:
    目的 拟通过病理学和生物化学方法研究甲苯对大鼠中枢神经系统的影响。

    方法 取健康成年雄性SD大鼠75只,随机分为5组,分别为空白对照组、赋形剂组、低剂量组(75 mg/kg体重)、中剂量组(150 mg/kg体重)和高剂量组(300 mg/kg体重)。采用腹腔注射的方法染毒,注射量为0.01 mL/g体重,隔日染毒1次;赋形剂组给予等体积橄榄油,空白对照组不加任何处理。染毒时间为30 d。染毒期满后,断头处死大鼠,取大脑皮层和海马,苏木素-伊红(HE)染色和超微结构检查;并取海马组织测定谷氨酸转运体的功能。

    结果 HE染色发现高剂量组皮层局部神经元及胶质细胞周围轻度空泡变性,部分血管间隙(VR腔)扩张增宽,高剂量组海马也可见部分神经元的空泡变性。神经元排列不规则,未见神经元和神经胶质细胞本身变性坏死。超微结构检查发现甲苯染毒组海马组织中神经元细胞膜不完整,细胞器(核糖体、高尔基体和线粒体)减少,线粒体脊萎缩,核固缩,核膜不完整,电子致密度增高,染色质呈凝聚团块状分布。皮层组织中部分血管内皮细胞核固缩,核膜不完整,呈凋亡样变化,对照组未发现有上述变化。高剂量组神经细胞谷氨酸转运体功能与对照组相比有明显下降(P<0.01),下降幅度达49%;其余染毒组与对照组相比,谷氨酸转运体功能差异无统计学意义。

    结论 甲苯可导致染毒大鼠的脑组织发生病理变化,谷氨酸转运体转运功能受抑制。

     

    Abstract:
    Objective To study the pathological and biochemical effect of toluene on the central nervous system of exposed rats.

    Methods Altogether 75 healthy male adult rats were chosen, and randomly devided into 5 groups (blank control group, excipient control group, low dose group, medium dose group and high dose group). With intraporitoneal administration of toluene(75 mg/kg body weight for low dose group, 150 mg/kg body weight for medium dose group, and 300 mg/kg body weight for high dose group) every other day for 30 d, the rats were killed, and their cortex and hippocampus were collected. Dyeing with heamatoxylin and eosin(HE), the specimens were observed under microscope and electron microscope for the pathological change of the brain. At the same time, the hippocampus was selected to measure the function of glutamate transporter of the brain.

    Results Microscopic observation showed that a light degeneration around neurons and gliacytes occurred in rats's cortex of high dose group and vessel rift(VR) became broadened. Vacuole degeneration happened around some hippocampal neurons of high dose group. Neurons arrayed irregularly, but no degeneration and necrosis were seen in the neurons and gliacytes. Electron microscope examination found that in the toluene exposed groups, nerve cells began apoptosis characterized with disintegration of cell membrane, decrease of organelle's amoun(t ribosome, Golgi body and mitochondria), withdrawing of mitochondrial ridges, nucleus pyknosis, discontinuation of nucleus's membrane, increase of electron density and mass distribution of chromatin. The apoptosis of blood endothelia cells was also found. No such changes were found in the control groups. Function of glutamate transporter of the nerve cells in the high dose group decreased by 49% significantly compared with that in control groups (P<0.01). The function of glutamate transporter in the other dose groups declined too but not significant compared with the control groups.

    Conclusion Toluene could induce the pathological change and decline of function of glutamate transporter in exposed rat's brain. Key Words:

     

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