Boeravinone B 通过抑制炎症和 JAK2/STAT3 信号通路对糖尿病肾病大鼠的肾脏保护作用

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-08-11 DOI:10.22074/cellj.2024.2017978.1468
Wenbin Wen, Jian Sun, Yanmei Ma, Shuaishuai Shi, Wei Zhang, Junyan Li, Huidan Guo
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引用次数: 0

摘要

目的:慢性炎症是糖尿病的常见特征,尤其是在血糖水平控制不佳的情况下。这种慢性低度炎症可影响包括肾脏在内的多个器官。荚膜细胞损伤在糖尿病肾病(DN)的发病过程中起着关键作用。本研究旨在评估 Boeravinone B(BB)对链脲佐菌素(STZ)诱导的大鼠 DN 的肾保护作用,并探讨其潜在机制:在本实验研究中,大鼠腹腔注射 STZ(60 mg/kg)诱导 DN。口服不同剂量的 BB(2.5、5 和 7.5 毫克/千克)。对葡萄糖水平、体重和器官重量(肝脏和肾脏)进行了评估。测定了肾脏、组织形态学、抗氧化剂、肝脏和细胞因子水平,以及 JAK2 和 STAT3 的 mRNA 表达水平。实验研究结束后,大鼠被处死,并取出肾组织进行组织病理学评估:结果:BB 治疗降低了血糖水平,增加了体重。结果:BB 治疗降低了葡萄糖水平,增加了体重,抑制了肝脏重量,增加了肾脏组织重量,还降低了尿酸、尿素、胆红素、肌酐(Cr)和白蛋白等肾脏参数。PJAK2、STAT3、RAGE、KIM-1、NAGL和S100A8均有所下降:通过减少氧化应激和炎症反应,服用 BB 对 STZ 诱导的大鼠 DN 具有肾脏保护作用。
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Renal Protective Effect of Boeravinone B against Diabetic Nephropathy Rats via Inhibition of The Inflammatory and JAK2/STAT3 Signalling Pathway.

Objective: Chronic inflammation is a common feature in diabetes, especially when blood sugar levels are poorly controlled. This chronic low-grade inflammation can affect various organs, including the kidneys. Podocyte damage play a key role in the development of diabetic nephropathy (DN). The aim of the study was to evaluate the nephroprotective effect of Boeravinone B (BB) against streptozotocin (STZ) induced DN in rats and explore the underlying mechanism.

Materials and methods: In this experimental study, the rats received intraperitoneal injections of STZ (60 mg/kg) to induce DN. Various doses of BB (2.5, 5, and 7.5 mg/kg) were administered orally. Glucose levels, body weights, and organ weights (hepatic and renal) were assessed. Renal, histomorphological, antioxidant, hepatic, and cytokine levels were determined, as were the mRNA expression levels of JAK2 and STAT3. At end of the experimental study, the rats were sacrificed and their renal tissues were removed for histopathological assessment.

Results: BB treatment decreased glucose levels and increased body weights. This treatment suppressed hepatic weights, increased renal tissue weights, and also decreased renal parameters like uric acid, urea, bilirubin, creatinine (Cr) and, albumin. There was a decrease (P<0.001) in histomorphological parameters such as kidney hypertrophy index (KHI), mean glomerular volume (MGV), foot process fusion ratio (FPFR), and glomerular basement membrane thickness (GBMT) after treatment with BB. In addition, this treatment improved the levels of renal podocin, renal CD2- associated protein (CD2AP) and suppressed hepatic parameter levels. BB treatment (P<0.001) altered antioxidant parameters and cytokine levels, and suppressed mRNA expressions of JAK2, STAT3, RAGE, KIM-1, NAGL, and S100A8.

Conclusion: Administration of BB showed renal protective effects against STZ-induced DN in rats via the reduction of oxidative stress and inflammatory reactions.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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