【作者】 刘玉香；

【导师】 孟紫强；

【作者基本信息】 山西大学 ， 环境科学， 2005， 硕士

【摘要】 二氧化硫（SO₂）是大气中最常见的大气污染物,其对呼吸道的刺激和损伤早已引起人们的关注。然而,近年来我室对SO₂的毒理学研究表明,SO₂是一种全身性毒物。为此,本次实验主要进行了以下几个方面的研究: 一、SO₂吸入对小鼠细胞因子水平的影响 为了探讨吸入不同浓度SO₂引起小鼠肺组织及血清中细胞因子的变化规律,利用ELISA法测定了SO₂吸入后（浓度为14、28、56mg/m³）小鼠肺组织及血清中细胞因子水平。结果表明:（1） 对于肺组织,当SO₂吸入浓度为14mg/m³时,IL-6、TNF-α的含量均显著升高（p<0.05）;吸入28mg/m³SO₂后,IL-6极显著升高（P<0.01）,TNF-α也显著升高（P<0.05）;吸入56ma/m³SO₂之后,肺组织中三种细胞因子均未见显著改变。（2） 对于血清,只有TNF-α在SO-2吸入浓度为14mg/m³时显著升高。表明SO₂的致炎作用主要发生在肺组织。所以测定肺组织细胞因子对于了解SO₂引起的肺损伤作用可能比血清更有价值。 二、SO₂吸入对小鼠肺、肝、脾超微结构的影响 为了了解SO₂吸入对小鼠肺、肝、脾超微结构的影响,对小鼠进行SO₂吸入（浓度为28、56、112mg/m³）染毒后,通过透射电镜观察发现: （1） SO₂吸入姐小鼠肺超微结构的改变主要表现为Ⅱ型肺泡上皮细胞的损伤:微绒毛减少,板层体空泡化,线粒体致密化或肿胀,细胞核及染色质也出现不同程度的病变;Ⅰ型肺泡上皮细胞线粒体空泡化,56mg/m³和112mg/m³组细胞核变形等。（2） SO₂吸入组小鼠肝细胞均有不同程度的病理改变,例如,线粒体轻度肿胀,核周隙不规则增宽,粗面内质网轻度扩张,胞质内有大小不等的脂滴出现;56mg/m³组小鼠肝细胞还出现核膜不清或完全消失,细胞器明显减少等坏死性病理改变;112mg/m³组小鼠肝细胞则伴随嗜酸性变、脂肪变及严重的坏死性病理改变。（3） SO₂吸入组小鼠脾脏的白髓区和红髓区淋巴细胞凋亡,呈现出一定的剂量依赖性。 三、SO₂吸入对小鼠睾丸、脑、心、肾超微结构的影响 为了了解SO₂吸入对小鼠睾丸、脑、心、肾超微结构的影响,对小鼠更多还原

【Abstract】 Sulfur dioxide （SO₂） is a major air pollutant all over the world. It can cause respiratory tract diseases such as tracheitis, asthma, emphysema, and has close relations with lung cancer. But many studies indicated that SO₂ is a systemic toxin, not only to respiratory system. So we studied the effects of SO₂ in the following aspects:First, in order to elucidate the immunotoxic mechanism exerted by sulfur dioxide （SO₂）, we investigated the effect of SO₂ on the cytokine levels in lungs and serum of male mice. Levels of interlukin-6 （IL-6） , tumor necrosis factor-α （TNF-α） , transforming growth factor- β1 （TGF-β1） in lungs and serum from male mice exposed to SO₂ at various concentrations （14, 28 and56mg/m³）were measured by the enzyme-linked immunosorbent assay. The results were as follows: （1） For lung tissues of male mice, expose to SO₂ at 14 mg/m³ caused statistically significant increase of levels of IL-6 and TNF-α （p<0.05） compared with the control group, at 28 mg/m³caused statistically highly significant increase of level of IL-6 （p<0.01） and significant increase of TNF-α （p<0.05）, at 56 mg/m³caused no any significant increase of levels of IL-6 and TNF-α. SO₂ at all concentrations tested could not cause significant change of level of TGF-β1 in lungs. （2） For serum from male mice, after expose to SO₂ at 14 mg/m³, level of TNF-α was significantly increased （p<0.05） compared with the control group, but the changes of levels of IL-6 and TGF-β1 were not significant. After expose to SO₂ at 28 mg/m³ and 56 mg/m³ , levels of IL-6 and TNF-a were increased non-significantly, but level of TGF-β1 was decreased non-significantly. These results imply that inflammation reaction could be induced in lung tissue by SO₂ inhalation and the inflammation reaction might relate to these cytokines. And determination of cytokines in lung may be more valuable than in serum when lung injury caused by SO₂.Second, to investigate the effect of sulfur dioxide inhalation on theultrastructure, the ultrastructures of the lungs, livers and spleens in mice were observed with electron microscopy after the mice were treated by SO2 inhalation （28, 56 and 112mg/m3）. The results were as follows: （1） It was found that type II alveolar cells of lungs in tested groups had obvious pathological changes including vacuolating of osmiophilic multilamellar bodies, decrease of microvillus , mitochondrial pyknosis or swelling and various changes of nucleus and chromatin. Meanwhile significant changes of mitochondrial and nucleus in type I alveolar cells were also observed. （2） A series of pathological changes were discovered in hepatic cells in tested groups, such as swelling of nucleus, dispersion of fatty droplets, degenerated mitochondria and dilation of rough endoplasmic reticulums etc; for SO2 exposure at 56mg/m3 the ultrastructure also showed necrosis of hepatocytes with unclear karyotheca or nearly dissolved karyotheca and decrease of organelle; for SO2 exposure at 112mg/m3 acid degeneration, fatty degeneration and severe necrosis of hepatocytes were found in addition to above changes. （3） Apoptotic number of splenocytes from mice exposed to SO2 was increased by SO2 inhalation in a dose-dependent manner.Finally, the ultrastructures of the testis, brains, hearts and kidneys in mice were also observed with electron microscopy after the mice were treated by SO2 inhalation （28 and 56 mg/m3）. The results were as follows: （1） Compared with control group, the basement membrane, various seminiferous cells, spermatozoa, sertoli cells of testis were changed in both tested groups. The changes of 56mg/m3 group were serious than the 28mg/m3 group. （2）In the tested groups, some of the cerebral cortex neurons, many glialcells and nerve fiber were damaged, Ihere was no significant difference between two tested groups. （3） It was found that mitochondrial swelling, decrease or disappearance of mitochondria crista, myocardial myofibril disorder, various changes of nucleus and chromatin, intercalated discs dissociation, endothelium edema in heart tissues in tested groups. In addition to above changes, myofibrillar fragmentation and dissolution, some myocardial cell membranes breach and inflammatory cell infiltration were observed in the更多还原