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吉格列汀对小鼠阿霉素诱导的肾病肾损伤的改善作用。

Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy.

作者信息

Kim Da Rae, Lee Shin Yeong, Kim Jin Sug, Kim Yang Gyun, Moon Ju-Young, Lee Sang Ho, Lee Tae Won, Ihm Chun Gyoo, Jeong Kyung Hwan

机构信息

Department of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.

Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.

出版信息

Biomed Res Int. 2017;2017:7275109. doi: 10.1155/2017/7275109. Epub 2017 Feb 23.

Abstract

. Previous studies have shown the antiapoptotic and anti-inflammatory potential of DPP-IV inhibitor in experimental models of renal injury. We tested whether DPP-IV inhibitor (gemigliptin) ameliorates renal injury by suppressing apoptosis, inflammation, and oxidative stress in mice with adriamycin nephropathy. . Mice were treated with normal saline (control), gemigliptin (GM), adriamycin (ADR), or adriamycin combined with gemigliptin (ADR+GM). Apoptosis, inflammation, and oxidative stress were analyzed via western blotting, real-time PCR, light microscopy, and immunofluorescence. . In the ADR+GM group, urine albumin creatinine ratio decreased significantly compared with that in the ADR group on day 15. Glomerulosclerosis index and tubulointerstitial injury index in mice with adriamycin-induced nephropathy decreased after gemigliptin treatment. ADR group showed higher levels of apoptosis, inflammation, and oxidative stress-related molecules compared with the control group. The upregulation of these molecules was significantly reduced by gemigliptin. In the ADR group, the staining intensities of WT-1 and nephrin reduced, but these changes were ameliorated in the ADR+GM group. . We demonstrated that gemigliptin ameliorates nephropathy by suppressing apoptosis, inflammation, and oxidative stress in mice administered adriamycin. Our data demonstrate that gemigliptin has renoprotective effects on adriamycin-induced nephropathy.

摘要

以往研究已在肾损伤实验模型中显示了二肽基肽酶 - Ⅳ(DPP - Ⅳ)抑制剂的抗凋亡和抗炎潜力。我们测试了DPP - Ⅳ抑制剂(吉格列汀)是否通过抑制阿霉素肾病小鼠的细胞凋亡、炎症和氧化应激来改善肾损伤。

小鼠分别用生理盐水(对照组)、吉格列汀(GM)、阿霉素(ADR)或阿霉素联合吉格列汀(ADR + GM)进行治疗。通过蛋白质免疫印迹法、实时聚合酶链反应、光学显微镜和免疫荧光分析细胞凋亡、炎症和氧化应激情况。

在第15天,ADR + GM组的尿白蛋白肌酐比值与ADR组相比显著降低。吉格列汀治疗后,阿霉素诱导的肾病小鼠的肾小球硬化指数和肾小管间质损伤指数降低。与对照组相比,ADR组凋亡、炎症和氧化应激相关分子水平更高。吉格列汀可显著降低这些分子的上调。在ADR组中,WT - 1和nephrin的染色强度降低,但在ADR + GM组中这些变化得到改善。

我们证明,吉格列汀通过抑制阿霉素给药小鼠的细胞凋亡、炎症和氧化应激来改善肾病。我们的数据表明,吉格列汀对阿霉素诱导的肾病具有肾脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceee/5343226/97df43a18979/BMRI2017-7275109.001.jpg

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