Juvenile Safety Testing For Chemicals And Pesticides

TOXICOLOGY LETTERS(2013)

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摘要
It is well known that somatostatin exerts a wide range of effects in the body, and acts as an autocrine or paracrine factor in the thymus. However, it has not been investigated yet whether somatostatin alters the thymus size and relation among the thymocyte subpopulations in the peripubertal rats. For this purpose, the peripubertal AO male rats were cannulated intracerebroventriculary and treated with repeated, low doses of somatostatin-14 (experimental group) or saline (control group). Twenty-four hours after the last treatment, we removed and prepared the thymuses for determination of thymocyte subpopulations by flow cytometry. After five days, animals were sacrificed and their thymuses taken for morphometrical analysis by stereological methods. We noticed that somatostatin-14 decreased volumes of thymus cortex and medulla, total number of thymocytes, number of thymocytes in the cortex and medulla and numerical density of thymocytes in deeper cortex. As a consequence of these changes, thymus size was also diminished. The phenotypic analysis of thymocyte subpopulations showed that somatostatin-14 decreased the percentage of CD4+CD8+ cells with low level of TCRαβ expression, positively selected CD4+CD8+TCRαβhigh cells and the most mature CD4−CD8+TCRαβhigh cells, while the percentage of CD4+CD8−TCRαβhigh thymocytes was slightly increased. Somatostatin-14 increased the relative proportion of the least mature CD4−CD8−TCRαβ−/low, CD4+CD8+TCRαβ− cells and both of TCRαβ−/low single positive subpopulations.These results show that centrally applied somatostatin-14, induces hypotrophy of the thymus in peripubertal rats by changing the volumes and cellularities of the thymic compartments. Additionally, increased number of the least mature thymocytes and a deficiency of double positive cells indicate the involvement of somatostatin in the modulation of T cells maturation.
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juvenile safety testing,chemicals
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