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在实验性糖尿病的膀胱中,依帕列净给药伴随有发育不良性尿路上皮改变。

Dysplastic urothelial changes accompany empagliflozin administration in urinary bladder of experimental diabetes.

机构信息

Department of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Department of Anatomy, Taibah College of Medicine, Taibah University, Taibah, Saudi Arabia.

出版信息

Int J Exp Pathol. 2019 Oct;100(5-6):369-377. doi: 10.1111/iep.12343. Epub 2020 Feb 10.

DOI:10.1111/iep.12343
PMID:32040227
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7042742/
Abstract

Empagliflozin (EMPA) is a promising novel antidiabetic drug; however, doubts have been raised regarding its use and the increased risk of urinary bladder carcinoma. In this study, we evaluated urothelium expression of cytokeratins (CKs) and Ki-67 proliferative activity in the urinary bladder of diabetic (DM + EMPA) and non-diabetic rats after EMPA administration. By routine histology, dysplastic changes were detected in the urothelium of diabetic as well as non-diabetic animals after EMPA administration. Moreover, the expression of CK-7 and CK-8 was significantly decreased (P < .05) while that of CK-20 as well as Ki-67 was significantly increased (P < .05) in EMPA per se and DM + EMPA urothelium groups compared to that of control and diabetics. The dysplastic changes together with the increased proliferative activity in urothelium after EMPA administration provide a cellular evidence that supports the former clinical concerns.

摘要

恩格列净(EMPA)是一种有前途的新型抗糖尿病药物;然而,人们对其使用和膀胱癌风险增加表示怀疑。在这项研究中,我们评估了 EMPA 给药后糖尿病(DM+EMPA)和非糖尿病大鼠膀胱的细胞角蛋白(CKs)表达和 Ki-67 增殖活性。通过常规组织学,在 EMPA 给药后,糖尿病和非糖尿病动物的尿路上皮均检测到发育不良改变。此外,与对照组和糖尿病组相比,EMPA 本身和 DM+EMPA 尿路上皮组中 CK-7 和 CK-8 的表达显著降低(P<.05),而 CK-20 和 Ki-67 的表达显著增加(P<.05)。EMPA 给药后尿路上皮的发育不良改变和增殖活性增加为支持先前临床关注的细胞证据提供了依据。

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本文引用的文献

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Diabetes Ther. 2019 Oct;10(5):1771-1792. doi: 10.1007/s13300-019-00686-z. Epub 2019 Aug 27.
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Effects of sodium-glucose cotransporter-2 inhibitors on the cardiovascular and renal complications of type 2 diabetes.钠-葡萄糖共转运蛋白 2 抑制剂对 2 型糖尿病心血管和肾脏并发症的影响。
Diabetes Obes Metab. 2020 Jan;22(1):16-29. doi: 10.1111/dom.13854. Epub 2019 Aug 30.
3
Increased mast cell number is associated with a decrease in beta-cell mass and regeneration in type 2 diabetic rats.肥大细胞数量的增加与 2 型糖尿病大鼠胰岛β细胞质量和再生的减少有关。
Acta Histochem. 2019 May;121(4):508-515. doi: 10.1016/j.acthis.2019.04.009. Epub 2019 Apr 20.
4
Sodium-glucose cotransporters: new targets of cancer therapy?钠-葡萄糖协同转运蛋白:癌症治疗的新靶点?
Arh Hig Rada Toksikol. 2018 Dec 1;69(4):278-285. doi: 10.2478/aiht-2018-69-3204.
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A study in a rat initiation-promotion bladder tumour model demonstrated no promoter/progressor potential of dapagliflozin.一项在大鼠起始促进膀胱肿瘤模型中的研究表明达格列净没有促进潜力。
Regul Toxicol Pharmacol. 2019 Apr;103:166-173. doi: 10.1016/j.yrtph.2019.01.031. Epub 2019 Jan 25.
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