家蚕粪便提取物改善腺嘌呤诱导的大鼠肾性贫血的可能机制。
Possible mechanisms by which silkworm faeces extract ameliorates adenine-induced renal anaemia in rats.
机构信息
Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Huazhong University of Science and Technology, No. 13, Hongkong Road, 430030, Wuhan, China.
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
出版信息
J Ethnopharmacol. 2021 Feb 10;266:113448. doi: 10.1016/j.jep.2020.113448. Epub 2020 Oct 3.
ETHNOPHARMACOLOGICAL RELEVANCE
Silkworm faeces are the dry faeces of the insect Bombyx mori (Linnaeus) and have historically been used in traditional Chinese medicine to treat blood deficiency and rheumatic pain. Silkworm faeces extract (SFE) is derived from silkworm faeces.
AIM OF THE STUDY
Clinical observations of patients in the Department of Nephrology have shown that SFE effectively improves renal anaemia. However, the molecular mechanism remains unclear. This article mainly explores the regulatory effects of SFE on erythropoietin (EPO) and hepcidin to identify the molecular mechanism of SFE.
MATERIALS AND METHODS
A rat model of renal anaemia was established by feeding rats food containing 0.75% adenine. SFE was orally administered to the rats, while recombinant human erythropoietin (rhEPO) was used as a positive control drug. Haematological parameters and inflammation levels were compared between rats from each group, and pathological kidney sections from each rat were observed. The serum EPO and hepcidin levels were detected using enzyme-linked immunosorbent assay (ELISA) kits, while Western blot analyses were performed to detect the levels of proteins involved in the EPO-related hypoxia-inducible factor 2α (HIF-2α)/prolyl hydroxylase 2 (PHD2) signalling pathway and hepcidin-related BMP6/SMAD4 and interleukin-6 (IL-6)/STAT3 signalling pathways.
RESULTS
SFE significantly ameliorated haematological parameters, renal function, and inflammation levels in the rats. A mechanistic study showed that SFE promoted EPO expression by upregulating HIF-2α expression and inhibiting the expression of NF-κB and GATA2 both in vivo and in vitro. In particular, SFE inhibited PHD2 expression, resulting in a decrease in the enzymatic reaction of HIF-2α to increase EPO expression. Furthermore, SFE inhibited hepcidin expression by blocking the BMP6/SMAD4 and IL-6/STAT3 pathways.
CONCLUSIONS
SFE regulated iron metabolism by inhibiting hepcidin and simultaneously promoted EPO synthesis to improve renal anaemia in rats.
民族药理学相关性
蚕沙是昆虫家蚕（Linnaeus）的干燥粪便，在传统中医中已被用于治疗血虚和风湿痛。蚕沙提取物（SFE）是从蚕沙中提取的。
研究目的
肾病科的临床观察表明，SFE 可有效改善肾性贫血。然而，其分子机制尚不清楚。本文主要探讨 SFE 对促红细胞生成素（EPO）和铁调素的调节作用，以确定 SFE 的分子机制。
材料与方法
通过给大鼠喂食含有 0.75%腺嘌呤的食物建立大鼠肾性贫血模型。给大鼠口服 SFE，重组人促红细胞生成素（rhEPO）作为阳性对照药物。比较各组大鼠的血液学参数和炎症水平，并观察每组大鼠的肾脏病理切片。采用酶联免疫吸附试验（ELISA）试剂盒检测血清 EPO 和铁调素水平，采用 Western blot 分析检测 EPO 相关缺氧诱导因子 2α（HIF-2α）/脯氨酰羟化酶 2（PHD2）信号通路和铁调素相关 BMP6/SMAD4 和白细胞介素 6（IL-6）/STAT3 信号通路相关蛋白的水平。
结果
SFE 可显著改善大鼠的血液学参数、肾功能和炎症水平。机制研究表明，SFE 通过上调 HIF-2α表达和抑制 NF-κB 和 GATA2 的表达，在体内和体外均促进 EPO 的表达。特别是，SFE 抑制 PHD2 的表达，从而减少 HIF-2α 的酶反应，增加 EPO 的表达。此外，SFE 通过阻断 BMP6/SMAD4 和 IL-6/STAT3 通路抑制铁调素的表达。
结论
SFE 通过抑制铁调素来调节铁代谢，同时促进 EPO 的合成，从而改善大鼠的肾性贫血。
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