首页> 外文期刊>Apoptosis: An international journal on programmed cell death >The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats
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The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats

机译:孕期接受免疫抑制治疗对雌性Wistar大鼠肾功能和自然肾细胞凋亡率的影响

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摘要

Pregnancy puts a significant additional strain on kidneys. The aim of our study was to investigate the impact of immunosuppressive drugs on changes in native kidneys in female Wistar rats after exposure during pregnancy. The study was conducted on 32 dams, subjected to immunosuppressive regimens commonly used in the therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; cyclosporine A, everolimus and prednisone). The animals received drugs for 2 weeks before pregnancy and during 3 weeks of pregnancy. In all treated dams lower body weight (but not kidney mass) and alterations in serum sodium and chloride ions were found; serum creatinine concentration was increased in dams treated with cyclosporine A, everolimus and prednisone. All treatment groups of dams showed increased apoptosis in the distal tubules. In histological examination the changed intensity of acidophilic or basophilic cytoplasm of epithelial cells was found in kidneys of rats treated with calcineurin inhibitors, mycophenolate mofetil and prednisone. All immunosuppressive regimens caused abnormalities affecting nephron tubules. Regimens containing calcineurin inhibitors and mycophenolate mofetil caused higher rate of apoptosis and more pronounced histopathological changes. Regimen based on everolimus despite the lower rate of apoptosis in the proximal tubules and lower accumulation of kidney injury markers revealed higher serum creatinine concentration. Thus, interpretation which combination of drugs is better or worse for long-lasting functioning of kidneys in pregnant females requires further studies.
机译:怀孕给肾脏带来了额外的负担。我们研究的目的是研究免疫抑制药物对怀孕后暴露于雌性Wistar大鼠体内天然肾脏变化的影响。该研究是在32个水坝上进行的,这些水坝接受了通常用于治疗人类肾脏移植受者的免疫抑制方案(环孢霉素A,霉酚酸酯和强的松;他克莫司,霉酚酸酯和泼尼松;环孢素A,依维莫司和泼尼松)。这些动物在怀孕前2周和怀孕3周期间接受药物治疗。在所有处理过的水坝中,体重均降低(但肾脏质量未降低),血清钠离子和氯离子也发生了变化。在用环孢霉素A,依维莫司和泼尼松治疗的大坝中,血清肌酐浓度升高。大坝的所有治疗组均显示远端小管细胞凋亡增加。在组织学检查中,发现在用钙调神经磷酸酶抑制剂,霉酚酸酯和强的松治疗的大鼠肾脏中,上皮细胞的嗜酸性或嗜碱性细胞质强度发生了改变。所有的免疫抑制方案都会引起异常,影响肾小管。含有钙调神经磷酸酶抑制剂和霉酚酸酯的方案导致更高的细胞凋亡率和更明显的组织病理学变化。尽管依维莫司的治疗方案尽管近端小管中的细胞凋亡率较低,并且肾脏损伤标记物的积累较低,但血清肌酐浓度较高。因此,对于孕妇的肾脏长效功能,哪种药物组合更好或更差的解释尚待进一步研究。

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