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阿魏酸通过改善自噬抑制糖尿病肾病小鼠炎症来改善肾损伤。

Ferulic acid ameliorates renal injury via improving autophagy to inhibit inflammation in diabetic nephropathy mice.

机构信息

Institution of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.

School of Basic Medicine, Guizhou University of traditional Chinese Medicine, Guiyang, Guizhou 550002, China.

出版信息

Biomed Pharmacother. 2022 Sep;153:113424. doi: 10.1016/j.biopha.2022.113424. Epub 2022 Jul 19.

Abstract

Diabetic nephropathy (DN) is one of the most serious microvascular complications following diabetes mellitus (DM). Ferulic acid (FA), a phenolic acid widely found in plants, has multiple pharmacological effects such as anti-oxidation, anti-inflammation and anti-tumor. However, the current research on FA in the field of DN is insufficient. The present study aimed to explore the nephroprotective effect of FA on DN in mice and reveal its underlying mechanism. DN was induced by high-fat diet (HFD) combined with streptozotocin (STZ) injection in male C57BL/6J mice. Animals were randomly divided into four groups (n = 8): Control group, DN group, FA group (200 mg/kg FA, i.g.) and valsartan (VAL) group (12 mg/kg VAL, i.g.). The drug was administered once a day for 8 weeks. Treated with FA, the body weight and fasting blood glucose (FBG) of DN mice were reduced and the renal organ coefficient was significantly optimized. Meanwhile, FA decreased levels of 24-h urine protein excretion (24-h UP) in urine and blood urea nitrogen (BUN), creatinine (Cr) in serum, reduced levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in serum. In addition, FA promoted light chain 3 (LC3) expression markedly, and inhibited the expressions of p62, NOD-like receptor family pyrin domain containing 3 (NLRP3) and interleukin-1β (IL-1β) in renal tissues. In conclusion, FA played a positive role in alleviating renal injury in HFD/STZ-induced DN mice by enhancing autophagy and suppressing excessive inflammation.

摘要

糖尿病肾病(DN)是糖尿病(DM)后最严重的微血管并发症之一。阿魏酸(FA)是一种广泛存在于植物中的酚酸,具有抗氧化、抗炎和抗肿瘤等多种药理作用。然而,目前 FA 在 DN 领域的研究还不够充分。本研究旨在探讨 FA 对糖尿病肾病小鼠的肾保护作用,并揭示其潜在机制。雄性 C57BL/6J 小鼠采用高脂肪饮食(HFD)联合链脲佐菌素(STZ)注射诱导 DN。动物随机分为四组(n=8):对照组、DN 组、FA 组(200mg/kg FA,ig)和缬沙坦(VAL)组(12mg/kg VAL,ig)。药物每天给药一次,持续 8 周。FA 治疗可降低 DN 小鼠的体重和空腹血糖(FBG),优化肾脏器官系数。同时,FA 降低了 24 小时尿蛋白排泄量(24 小时 UP)、血清血尿素氮(BUN)和肌酐(Cr)水平,降低了血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平。此外,FA 明显促进了轻链 3(LC3)的表达,并抑制了肾脏组织中 p62、NOD 样受体家族 pyrin 结构域包含 3(NLRP3)和白细胞介素-1β(IL-1β)的表达。综上所述,FA 通过增强自噬和抑制过度炎症,对 HFD/STZ 诱导的 DN 小鼠的肾损伤发挥了积极作用。

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