关键词: 吡哆胺, 血管紧张素Ⅱ, 糖基化终末产物, 细胞凋亡, 纤维化

Abstract: Objective To investigate the effect and the mechanism of pyridoxamine on apoptosis and fibrogenic factors expression in HK-2 cells. Methods Cells were divided into groups as follows: control, AngⅡ(10-6 mol/L ), AngⅡ+ T(10-5 mol/L) , AngⅡ+ P(0.01、0.1、1、10mmol/L) , AngⅡ+ T+P (1mmol/L) . Cell viability was evaluated by MTT. Cell apoptosis was detected by AnnexinV-FITC/PI assay. Intracellular reactive oxygen species (ROS) was measured by flow cytometry. AGEs level in cellular supernatant were determined by ELISA. The real-time PCR was applied for the mRNA expression of RAGE, TGF-???? CTGF and MMP-9. The RAGE, TGF-????CTGF and p-NF-κBP65 expression were analyzed by Western Blot. Results Compared with AngⅡ,pyridoxamine and telmisartan increased cell viability, inhibited cell apoptosis, decreased intercellular ROS level, and lowered the AGEs level in cell culture supernatant（all P﹤0.01）. The mRNA and protein expression of RAGE, TGF-β1, CTGF, MMP-9 and NF-κBP65 phosphorylation were down-regulated respectively（all P﹤0.01）. These effects were more pronounced in pyridoxamine groups than telmisartan group（P﹤0.05 or P﹤0.01）while the combination group exhibited more significant effects than the single use of telmisartan（all P﹤0.01）. Conclusion Pyridoxamine may inhibit cell apoptosis and down-regulate fibrogenic factors expression through AGEs-RAGE inhibition, oxidative stress alleviation and NF-κB inactivation.

Key words: pyridoxamine, angiotensin , advanced glycation end products, apoptosis, fibrosis