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长期免疫抑制治疗对大鼠原生肝脏形态及肝细胞凋亡的影响

Effect of long-term immunosuppressive therapy on native rat liver morphology and hepatocyte- apoptosis.

作者信息

Wilk Aleksandra, Szypulska-Koziarska Dagmara, Kędzierska-Kapuza Karolina, Kolasa-Wołosiuk Agnieszka, Misiakiewicz-Has Kamila, Ciechanowski Kazimierz, Wiszniewska Barbara

机构信息

Department of Histology and Embryology, Pomeranian Medical University, Szczecin, Poland.

Department of Histology and Embryology, Pomeranian Medical University, Szczecin, Poland.

出版信息

Transpl Immunol. 2018 Oct;50:1-7. doi: 10.1016/j.trim.2018.05.001. Epub 2018 May 16.

DOI:10.1016/j.trim.2018.05.001
PMID:29777763
Abstract

A negative result of therapy based on immunosuppressive drugs is its leading to pathological alterations in the organ, including liver. Use of immunosuppressive medication may also lead to organized and genetically controlled cell death - apoptosis. The aim of this study was to examine histopathological changes in the livers of rats treated with immunosuppressive drugs, and also to determine the effects of different groups of immunosuppressive drugs on apoptosis activity in the hepatocytes of rat livers. The study was conducted on archival material obtained from Department of Nephrology, Transplantology and Internal Medicine of the Independent Public Clinical Hospital No. 2 at the Pomeranian Medical University in Szczecin, Poland. Statistical comparison of the treatment groups showed that all groups with rapamycin (sirolimus)-based regimens: Tacrolimus, Rapamycin, Glucocorticosteroid (TRG); Cyclosporine, Rapamycin, Glucocorticosteroid (CRG); Mycophenolate, Rapamycin, Glucocorticosteroid (MRG) and additionally Cyclosporine, Mycophenolate, Glucocorticosteroid (CMG) exhibited significantly more pronounced apoptosis than the control group, with p < 0.01, p < 0.05, p < 0.01 and p < 0.01, respectively. Furthermore, in the TRG group, over 90% of apoptotic hepatocytes were seen in the examined classic lobules. Additionally, every liver from treatment group was pathologically altered, including dilated sinusoids, pyknotic nuclei, swollen walls of the vessels. Long-lasting immunosuppressive treatment affects the liver both in terms of histological changes within the structure of the liver and in terms of the percentage of apoptotic hepatocytes. The following study seems to be very innovating due to the duration of the experiment and used drugs-protocols, since they reflect human treatment.

摘要

基于免疫抑制药物的治疗的一个负面结果是其会导致包括肝脏在内的器官发生病理改变。使用免疫抑制药物也可能导致有组织的、基因控制的细胞死亡——细胞凋亡。本研究的目的是检查用免疫抑制药物治疗的大鼠肝脏的组织病理学变化,并确定不同组别的免疫抑制药物对大鼠肝脏肝细胞凋亡活性的影响。该研究是基于从波兰什切青波美拉尼亚医科大学第二独立公共临床医院肾脏病、移植学和内科获取的存档材料进行的。治疗组的统计比较表明,所有基于雷帕霉素(西罗莫司)方案的组:他克莫司、雷帕霉素、糖皮质激素(TRG);环孢素、雷帕霉素、糖皮质激素(CRG);霉酚酸酯、雷帕霉素、糖皮质激素(MRG)以及另外的环孢素、霉酚酸酯、糖皮质激素(CMG),与对照组相比均表现出明显更显著的细胞凋亡,p值分别为<0.01、<0.05、<0.01和<0.01。此外,在TRG组中,在所检查的经典肝小叶中可见超过90%的凋亡肝细胞。另外,治疗组的每只肝脏均发生了病理改变,包括肝血窦扩张、核固缩、血管壁肿胀。长期的免疫抑制治疗在肝脏结构的组织学变化以及凋亡肝细胞的百分比方面都会影响肝脏。鉴于实验的持续时间和所使用的药物方案,以下研究似乎非常具有创新性,因为它们反映了人类治疗情况。

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