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甘草素减轻糖基化终产物对肾近端肾小管上皮细胞的毒性作用。

Isoliquiritigenin ameliorates advanced glycation end-products toxicity on renal proximal tubular epithelial cells.

机构信息

Ph.D. Program for Aging, Taichung, Taiwan.

Department of Chinese Medicine, Yuan Sheng Hospital, Chang Hua, Taiwan.

出版信息

Environ Toxicol. 2022 Aug;37(8):2096-2102. doi: 10.1002/tox.23553. Epub 2022 May 18.

DOI:10.1002/tox.23553
PMID:35583127
Abstract

Diabetic nephropathy is a serious chronic complication affecting at least 25% of diabetic patients. Hyperglycemia associated advanced glycation end-products (AGEs) increase tubular epithelial-myofibroblast transdifferentiation (TEMT) and extracellular matrix synthesis and thereby causes renal fibrosis. The chalcone isoliquiritigenin, found in many herbs of Glycyrrhiza family, is known for potential health-promoting effects. However, their effects on AGE-associated renal proximal tubular fibrosis are not known yet. In this study, the effect of isoliquiritigenin on AGE-induced renal proximal tubular fibrosis was determined in cultured HK-2 cell line. The results show that 200 μg/mL of AGE-induced TEMT and the formed myofibroblasts synthesized collagen to increase extracellular matrix formation thereby lead to renal tubular fibrosis. However, treatment with 200 nM of isoliquiritigenin considerably inhibited the TEMT and suppressed the TGFβ/STAT3 mechanism to inhibit collagen secretion. Therefore, isoliquiritigenin effectively suppressed AGE-induced renal tubular fibrosis.

摘要

糖尿病肾病是一种严重的慢性并发症,至少影响 25%的糖尿病患者。与高血糖相关的晚期糖基化终产物 (AGEs) 会增加肾小管上皮细胞-肌成纤维细胞转分化 (TEMT) 和细胞外基质的合成,从而导致肾纤维化。查尔酮异甘草素是甘草属多种草药中的一种成分,具有潜在的促进健康的作用。然而,其对 AGE 相关的肾近端小管纤维化的影响尚不清楚。在这项研究中,在体外培养的 HK-2 细胞系中,确定了异甘草素对 AGE 诱导的肾近端小管纤维化的作用。结果表明,200μg/ml 的 AGE 诱导的 TEMT 和形成的肌成纤维细胞合成胶原,增加细胞外基质形成,从而导致肾小管纤维化。然而,用 200nM 的异甘草素处理可显著抑制 TEMT,并抑制 TGFβ/STAT3 机制以抑制胶原分泌。因此,异甘草素能有效抑制 AGE 诱导的肾小管纤维化。

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