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改善肾病模型肾脏中 LXR 介导的脂质代谢,同时抑制炎症和纤维化。

Improvement of LXR-mediated lipid metabolism in nephrotic model kidney accompanied by suppression of inflammation and fibrosis.

机构信息

Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga Ward, Shizuoka, Shizuoka, 422-8526, Japan; Iwate Medical University, School of Pharmacy, Health Chemistry, 1-1-1 Idaiodori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.

Iwate Medical University, School of Pharmacy, Health Chemistry, 1-1-1 Idaiodori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan; Iryo Sosei University, Faculty of Pharmacy, 5-5-1, Chuodai Iino, Iwaki, Fukushima, 970-8551, Japan.

出版信息

Biochem Biophys Res Commun. 2023 Jul 23;666:122-127. doi: 10.1016/j.bbrc.2023.05.019. Epub 2023 May 4.

Abstract

Kidney disease affects millions of people worldwide. Chronic kidney diseases, such as diabetic nephropathy, are often accompanied by nephrotic syndrome, which causes a large amount of protein and lipid to leak out into the urine. Leaked lipids are well known to accumulate in the proximal tubules as lipid droplets. However, the role of lipid metabolism in the kidney has not been thoroughly studied, and the relationship between accumulated lipid and pathological progression is often unknown. In this study, we showed that reducing accumulated lipids by exerting an agonistic effect on Liver X receptor, one of the nuclear receptors known to play an important role in lipid metabolism, suppressed the development of pathological conditions, such as inflammation and fibrosis, in a nephrosis model. Until now, many renal disease treatments have focused on suppressing the inflammatory response. However, it is now clear that even if the direct anti-inflammatory response is weak, the spread of inflammation and fibrosis can be suppressed by reducing accumulated lipids. Our results suggest that reducing abnormal lipid accumulation in the kidney could lead to disease treatment.

摘要

肾病影响着全球数百万人。慢性肾脏病,如糖尿病肾病,常伴有肾病综合征,导致大量蛋白质和脂质漏入尿液。众所周知,漏出的脂质会在近端肾小管中以脂滴的形式积累。然而,脂质代谢在肾脏中的作用尚未被彻底研究,积累的脂质与病理进展之间的关系通常也不清楚。在这项研究中,我们通过对核受体肝 X 受体(已知在脂质代谢中起重要作用的核受体之一)发挥激动作用来减少积累的脂质,抑制了肾病模型中炎症和纤维化等病理状况的发展。到目前为止,许多肾脏疾病的治疗方法都集中在抑制炎症反应上。然而,现在很明显,即使直接的抗炎反应较弱,通过减少积累的脂质也可以抑制炎症和纤维化的扩散。我们的研究结果表明,减少肾脏中异常脂质的积累可能会导致疾病的治疗。

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