糖化白蛋白调控肾损伤相关分子与Toll样受体信号通路及齐墩果酸对其干预作用的研究

doi:10.3969/j.issn.1006-7795.2019.04.021

首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (4): 609-614.doi: 10.3969/j.issn.1006-7795.2019.04.021

糖化白蛋白调控肾损伤相关分子与Toll样受体信号通路及齐墩果酸对其干预作用的研究

段楠, 黄辰炜, 逄璐, 李海霞

北京大学第一医院检验科, 北京 100034

收稿日期:2019-01-10 出版日期:2019-07-21 发布日期:2019-07-19
通讯作者: 李海霞 E-mail:leehaixia@139.com
基金资助:
北京大学第一医院科研种子基金（2019SF35）。

Glycated albumin regulates renal injury-associated molecules and Toll-like receptor signaling pathway and the intervention effect of oleanolic acid

Duan Nan, Huang Chenwei, Pang Lu, Li Haixia

Department of Clinical Laboratory, Peking University First Hospital, Beijing 100034, China

Received:2019-01-10 Online:2019-07-21 Published:2019-07-19
Supported by:
This study was supported by Scientific Research Seed Fund of Peking University First Hospital(2019SF35).

摘要/Abstract

摘要： 目的探讨人近端肾小管上皮细胞（HK-2细胞系）在糖化白蛋白（glycated albumin，GA）与齐墩果酸（oleanolic acid，OA）作用下，肾损伤分子-1（kidney injury molecule-1，KIM-1）、中性粒细胞明胶酶相关载脂蛋白（neutrophil gelatinase-associated lipocalin，NGAL）及Toll样受体信号通路相关分子的表达情况。方法采用GA及OA处理HK-2细胞24 h，real-time PCR检测KIM-1、NGAL以及p38丝裂原活化蛋白激酶（mitogen activated protein kinase，MAPK）、白细胞介素-1受体相关激酶4（interleukin-1 receptor-associated kinase 4，IRAK4）、Toll样受体（Toll-like receptor，TLR）1、TLR2、TLR7和TLR9的mRNA表达，ELISA法检测细胞上清液KIM-1与NGAL水平，Western blotting法检测细胞内p38 MAPK、IRAK4、TLR1、TLR2、TLR7和TLR9蛋白表达。结果与对照组比较，GA能显著上调KIM-1、NGAL mRNA与蛋白的含量（P<0.05），并促进p38 MAPK、IRAK4、TLR1、TLR2 mRNA及蛋白的表达（P<0.05）；加入OA能显著抑制上述作用（P<0.05）。结论 GA能够上调KIM-1和NGAL的表达与释放，激活Toll样受体信号通路，对人近端肾小管上皮细胞造成损伤；而加入OA能够有效干预GA调控的损伤。

关键词: 糖化白蛋白, 齐墩果酸, Toll样受体信号通路, 肾损伤分子-1, 中性粒细胞明胶酶相关载脂蛋白

Abstract: Objective To investigate the effects of glycated albumin (GA) and oleanolic acid (OA) on the expression of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and some molecules of Toll-like receptor (TLR) signaling pathway in human proximal tubular epithelial cells (HK-2 cells). Methods The HK-2 cells were treated with GA, GA and OA for 24 h. The mRNA levels of KIM-1, NGAL, p38 mitogen activated protein kinase (MAPK), interleukin-1 receptor-associated kinase 4 (IRAK4), TLR 1, TLR2, TLR7 and TLR9 were detected by real-time PCR. The releases of KIM-1 and NGAL in the supernatants were detected by ELISA. The protein levels of p38 MAPK, IRAK4, TLR1, TLR2, TLR7 and TLR9 were measured by Western blotting. Results Compared with control group, GA could significantly up-regulate the mRNA and the protein levels released in supernatants of KIM-1 and NGAL (P<0.05), and promoted the expression of p38 MAPK, IRAK4, TLR1, TLR2 mRNA and protein in HK-2 cells (P<0.05). OA treatment could significantly inhibit theses effects (P<0.05). Conclusion GA can up-regulate the expression and release of KIM-1 and NGAL, and activate the TLR signaling pathway, suggesting that GA could play an important role in regulating renal injury. OA had effective intervention effect on GA.

Key words: glycated albumin, oleanolic acid, Toll-like receptor signaling pathway, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin

中图分类号:

R692.6

段楠, 黄辰炜, 逄璐, 李海霞. 糖化白蛋白调控肾损伤相关分子与Toll样受体信号通路及齐墩果酸对其干预作用的研究[J]. 首都医科大学学报, 2019, 40(4): 609-614.

Duan Nan, Huang Chenwei, Pang Lu, Li Haixia. Glycated albumin regulates renal injury-associated molecules and Toll-like receptor signaling pathway and the intervention effect of oleanolic acid[J]. Journal of Capital Medical University, 2019, 40(4): 609-614.

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糖化白蛋白调控肾损伤相关分子与Toll样受体信号通路及齐墩果酸对其干预作用的研究

Glycated albumin regulates renal injury-associated molecules and Toll-like receptor signaling pathway and the intervention effect of oleanolic acid

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