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用于早期检测糖尿病肾病的新型生物标志物的鉴定

Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy.

作者信息

Kim Kyeong-Seok, Lee Jin-Sol, Park Jae-Hyeon, Lee Eun-Young, Moon Jong-Seok, Lee Sang-Kyu, Lee Jong-Sil, Kim Jung-Hwan, Kim Hyung-Sik

机构信息

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea.

出版信息

Biomedicines. 2021 Apr 22;9(5):457. doi: 10.3390/biomedicines9050457.

Abstract

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

摘要

糖尿病肾病(DN)是糖尿病最常见的并发症之一。DN发生后,患者会进展为终末期肾病,这与高发病率和高死亡率相关。在此,我们开发了早期诊断生物标志物来检测DN,作为DN干预的一种策略。对于DN模型,采用Zucker糖尿病脂肪大鼠进行DN表型分析。结果显示,DN大鼠的血糖、血尿素氮(BUN)和血清肌酐水平显著升高,伴有严重的肾损伤、纤维化和微观结构变化。此外,DN大鼠的肾损伤分子-1(KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的尿排泄量显著增加。转录组分析显示,鉴定出了新的DN生物标志物,如补体成分4b(C4b)、补体因子D(CFD)、C-X-C基序趋化因子受体6(CXCR6)和白血病抑制因子(LIF)。此外,在DN患者的尿液中也发现了这些生物标志物。由于这些生物标志物在DN大鼠的尿液和肾脏以及糖尿病患者的尿液中均被检测到,因此所选标志物可作为慢性糖尿病肾病的早期诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec49/8146473/539beae0a2fb/biomedicines-09-00457-g001.jpg

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