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铁皮石斛多糖通过 LncRNA XIST/TGF-β1 延缓糖尿病肾病间质纤维化。

Polysaccharides from Dendrobium officinale delay diabetic kidney disease interstitial fibrosis through LncRNA XIST/TGF-β1.

机构信息

Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550002, China; Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China; NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China; The Second Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang, Guizhou 550001, China.

Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China; NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, China; Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Centre for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China.

出版信息

Biomed Pharmacother. 2024 Jun;175:116636. doi: 10.1016/j.biopha.2024.116636. Epub 2024 Apr 26.

Abstract

PURPOSE

Renal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis.

METHODS

Using db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-β1, and renal interstitial fibrosis-related molecules.

RESULTS

DOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-β1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD.

CONCLUSION

DOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-β1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

摘要

目的

肾间质纤维化是糖尿病肾病(DKD)进展的病理表现。铁皮石斛多糖(DOP)是铁皮石斛的主要活性成分之一,具有降血糖和降血脂作用,临床上用于治疗糖尿病。然而,DOP 延缓 DKD 进展的作用尚不清楚。本研究旨在探讨 DOP 延缓 DKD 肾间质纤维化的潜在机制。

方法

采用 db/db 小鼠作为 DKD 模型,通过灌胃给予 DOP,并观察其治疗效果。采用 ASO 技术敲低肾组织中 lncRNA XIST 的表达,检测 lncRNA XIST、TGF-β1 及肾间质纤维化相关分子的表达。

结果

DOP 主要由单糖组成,其中葡萄糖占 91.57%,甘露糖占 1.41%,呈类球形结构。其具有较高的多分散指数,Mw/Mn 为 6.146,多糖主要通过 4-Man(p)和 4-Glc(p)键连接。在 db/db 小鼠的肾脏中,lncRNA XIST 和 TGF-β1 表达较高;然而,经 DOP 胃内灌注后,其表达明显降低,而敲低 lncRNA XIST 后,可能会延缓 DKD 肾间质纤维化的进展。

结论

DOP 可能通过调节 LncRNA XIST/TGF-β1 相关纤维化通路来延缓 DKD 肾间质纤维化的进展。这为临床延缓 DKD 肾间质纤维化进展的策略提供了新视角。

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