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维生素D对阿霉素诱导的肾病中肾脏组织学及瞬时受体电位香草酸亚型1(TRPV1)通道的影响

Effects of vitamin D on kidney histology and trpv1 channels in doxorubicin-induced nephropathy.

作者信息

Gurel Ali, Atli Hasan, Kaya Nalan, Onalan Ebru, Kuloglu Tuncay, Aygen Bilge

机构信息

Nephrology Department, Mengucek Gazi Training and Research Hospital Erzincan, Turkey.

Internal Medicine Department, Firat University Medical School Elazig, Turkey.

出版信息

Int J Clin Exp Med. 2015 Aug 15;8(8):13548-55. eCollection 2015.

PMID:26550293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4612978/
Abstract

Doxorubicin (DXR) is an antineoplastic agent of the anthracycline group, and may show nephrotoxic effects in animal models and humans. We investigated changes in kidney tissue following doxorubicin treatment and the effects of vitamin D on kidney tissue and TRPV1 channels. In this study, 24 adult male Wistar Albino rats were used. The animals were divided into four groups of six animals. During the 14-day experiment period, Group I did not have any application. 200 IU/day cholecalciferol was administered orally to Group II. Group III received 10 mg/kg single dose of DXR intraperitoneally (IP); and Group IV had a single 10 mg/kg dose of IP DXR and 200 IU/day of oral cholecalciferol. At the end of the experiment, the rats were decapitated, and their kidney tissues were removed. TRPV1 expression and apoptosis were detected in the tissue section by using immunohistochemical, TUNEL and real time-PCR (RT-PCR) techniques. The findings were examined and photographed with BH2 Olympus photomicroscope. As result of immunohistochemical staining, RT-PCR and examination with light microscope, it was found that the TRPV 1 immunoreactivity of the DXR group decreased in comparison with the control group, and the vitamin D application did not reverse this effect. Apoptosis detected by the TUNEL method tended to increase in the doxorubicin group and was relatively reversed with the administration of vitamin D. Tissue malondialdehyde (MDA) levels were observed to correlate with the findings of apoptosis. This study showed that vitamin D has anti- apoptotic and antioxidant effects on kidney tissue after DXR-induced injury.

摘要

阿霉素(DXR)是一种蒽环类抗肿瘤药物,在动物模型和人类中可能表现出肾毒性作用。我们研究了阿霉素治疗后肾组织的变化以及维生素D对肾组织和瞬时受体电位香草酸亚型1(TRPV1)通道的影响。在本研究中,使用了24只成年雄性Wistar白化大鼠。将动物分为四组,每组6只。在为期14天的实验期间,第一组未进行任何处理。第二组口服给予200国际单位/天的胆钙化醇。第三组腹腔注射(IP)10毫克/千克单剂量阿霉素;第四组腹腔注射10毫克/千克单剂量阿霉素并口服200国际单位/天的胆钙化醇.实验结束时,将大鼠断头并取出其肾组织。通过免疫组织化学、末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)和实时聚合酶链反应(RT-PCR)技术检测组织切片中的TRPV1表达和细胞凋亡。用奥林巴斯BH2显微镜检查并拍摄结果。免疫组织化学染色、RT-PCR和光学显微镜检查结果显示,与对照组相比,阿霉素组的TRPV1免疫反应性降低,维生素D的应用并未逆转这种效应。TUNEL法检测的细胞凋亡在阿霉素组中趋于增加,而维生素D给药后相对逆转。观察到组织丙二醛(MDA)水平与细胞凋亡结果相关。本研究表明,维生素D对阿霉素诱导损伤后的肾组织具有抗凋亡和抗氧化作用。

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