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槲皮素通过抑制HMGB1/RAGE/NF-κB信号通路改善大鼠糖尿病肾损伤

[Quercetin ameliorates diabetic kidney injury in rats by inhibiting the HMGB1/RAGE/NF-κB signaling pathway].

作者信息

Jiang Y, Li X, Geng J, Chen Y, Tang B, Kang P

机构信息

School of Clinical Medicine, Bengbu Medical University, Bengbu 233000, China.

Department of Cardiovascular Medicine of First Affiliated Hospital, Bengbu Medical University, Bengbu 233000, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2024 Sep 20;44(9):1769-1775. doi: 10.12122/j.issn.1673-4254.2024.09.17.

Abstract

OBJECTIVE

To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms.

METHODS

Twenty-four adult male SD rats were randomized equally into normal control group, high-glucose and high-fat feeding group, streptozotocin (STZ) -induced diabetic model group, and quercetin treatment (daily dose 100 mg/kg) group. Pathological changes of the renal tissues of the rats were observed with HE staining, serum inflammatory factor levels were determined with ELISA, and renal expression of NF‑κB was observed by immunohistochemistry. Fast blood glucose (FBG), serum levels of triglyceride (TG), BUN, and Scr, and 24-h urine protein content of the rats were measured, and renal expressions of HMGB1, RAGE, NF‑κB, Bax, Bcl-2, and caspase-3 were detected with Western blotting.

RESULTS

The diabetic rats showed significantly increased levels of FBG, TG, BUN, and Scr, renal hypertrophy index, 24-h urinary protein content, serum IL-1β, IL-6 and TNF-α levels and renal expressions HMGB1, RAGE, NF‑κB, Bax, and caspase-3 with decreased renal expression of Bcl-2. All these changes were significantly alleviated by quercetin treatment of the rats.

CONCLUSION

Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.

摘要

目的

探讨槲皮素对糖尿病大鼠肾脏炎症和细胞凋亡的影响及其可能机制。

方法

将24只成年雄性SD大鼠随机均分为正常对照组、高糖高脂喂养组、链脲佐菌素(STZ)诱导的糖尿病模型组和槲皮素治疗组(每日剂量100 mg/kg)。采用HE染色观察大鼠肾组织病理变化,ELISA法检测血清炎症因子水平,免疫组化法观察肾组织中NF-κB的表达。检测大鼠空腹血糖(FBG)、血清甘油三酯(TG)、尿素氮(BUN)、肌酐(Scr)水平及24小时尿蛋白含量,Western blotting法检测肾组织中HMGB1、RAGE、NF-κB、Bax、Bcl-2和caspase-3的表达。

结果

糖尿病大鼠的FBG、TG、BUN、Scr水平、肾肥大指数、24小时尿蛋白含量、血清IL-1β、IL-6和TNF-α水平以及肾组织中HMGB1、RAGE、NF-κB、Bax和caspase-3的表达均显著升高,而Bcl-2的肾组织表达降低。槲皮素治疗大鼠后,所有这些变化均得到显著缓解。

结论

槲皮素可能通过抑制HMGB1/RAGE/NF-κB炎症信号通路减轻糖尿病大鼠肾损伤,从而减轻肾脏炎症和肾细胞凋亡。

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Therapeutic transformation for diabetic kidney disease.糖尿病肾病的治疗转变。
Kidney Int. 2021 Feb;99(2):301-303. doi: 10.1016/j.kint.2020.10.003.

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