索非布韦(Sovaldi)对成年雄性白化大鼠基底粘膜的影响及岩藻糖聚糖可能的保护作用:组织学、组织化学和免疫组织化学研究

D. El-ghazouly, R. Yassien
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引用次数: 2

摘要

背景:索非布韦是治疗慢性丙型肝炎病毒感染的一种有希望的药物。然而,它记录了对胃肠道的一些不利影响。岩藻糖聚糖是一种硫酸盐酸化多糖,除具有抗炎和抗氧化作用外,还具有细胞保护作用。目的:研究索非布韦对基底粘膜的可能影响,并评价岩藻糖聚糖可能的保护作用。材料与方法:将40只成年雄性白化病大鼠平均分为4组,每天给药1次,连续5周。对照组(一):给予蒸馏水和生理盐水。岩藻糖聚糖组(II):给予80 mg/kg。索非布韦组(III):给药4 mg/kg。IV组:给予岩藻多糖和索非布韦,剂量与前几组相同。所有大鼠在最后一次给药后1天处死。取胃标本进行光镜和电镜检查。结果:索非布韦治疗后大鼠基底窝扩张,基底腺囊性扩张,上皮上皮变平。壁细胞细胞质空泡化,细胞核收缩。主要细胞粗面内质网扩张,分泌颗粒减少。固有层可见炎性细胞浸润,血管充血,红细胞外渗。统计上,胶原纤维的面积%有极显著的上升,而周期性酸性席夫-阿利新蓝染色(PAS-AB)反应的面积%有极显著的下降。免疫组化结果显示增殖细胞核抗原(PCNA)表达明显增加。岩藻多糖与索非布韦联合使用可使这些变化最小化。结论:索非布韦可引起基底粘膜的组织学改变,褐藻糖丹可减轻索非布韦的组织学改变。
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Effect of Sofosbuvir (Sovaldi) on the fundic mucosa of adult male albino rats and the possible protective role of Fucoidan: Histological, histochemical, and immunohistochemical study
Background: Sofosbuvir (SOF) is a hopeful remedy for chronic hepatitis C virus infection. However, it records some unfavorable influences on gastrointestinal tract. Fucoidan is a sulfated polysaccharide having cytoprotective effect besides anti-inflammatory and antioxidant properties.Aim: This work has been focused on the possible effect of sofosbuvir on the fundic mucosa and to assess the probable role of protection of fucoidan.Materials and methods: we divided 40 adult male albino rats equally into four groups and were received drugs as a single daily dose for five weeks. Control group (I): were received distilled water and normal saline. Fucoidan group (II): were received 80 mg/kg. Sofosbuvir group (III): were received 4 mg/kg. Group IV: were received Fucoidan and Sofosbuvir with the same doses as pervious groups. All rats were sacrificed one day following the last dose. Stomach specimens were obtained and prepared for light and electron microscopic examination.Results: Sofosbuvir-treated rats showed dilated fundic pits and cystic dilatation of fundic glands with flattening of their epithelial lining. Vacuolation of cytoplasm and shrunken pyknotic nuclei were detected in parietal cells. Dilatation of rough endoplasmic reticulum and loss of secretory granules were detected in the chief cells. Infiltration of inflammatory cells with congested blood vessels and extravasated RBCs were detected in lamina propria. Statistically, there was a highly significant rise in the area% of collagen fibers while area% of Periodic Acid Schieff -Alcian Blue stain (PAS–AB) reaction showed a highly significant reduction comparing with the control. The immunohistochemical results revealed marked increase in proliferating cell nuclear antigen (PCNA) expressions. The administration of Fucoidan with Sofosbuvir minimized these changes.Conclusion: Sofosbuvir has been proved to induce histological changes in the fundic mucosa and these changes can be attenuated by Fucoidan when given in concomitant with it.
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