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葛根素通过Nrf2/HO-1途径抑制细胞凋亡和内质网应激来减轻肾缺血/再灌注损伤。

Puerarin alleviates renal ischemia/reperfusion injury by inhibiting apoptosis and endoplasmic reticulum stress via Nrf2/HO-1 pathway.

作者信息

Wang Jingsong, Zheng Qingyuan, Chen Zhiyuan, Liu Xiuheng, Wan Shanshan, Wang Lei

机构信息

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.

Institute of Urologic Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.

出版信息

Iran J Basic Med Sci. 2025;28(2):187-193. doi: 10.22038/ijbms.2024.80438.17412.

Abstract

OBJECTIVES

To explore the effects of puerarin on renal ischemia/reperfusion injury and the possible mechanism.

MATERIALS AND METHODS

The experimental mice were injected with puerarin (50 or 100 mg/kg) per day or equal sterile saline by intraperitoneal injection for one week, and a renal I/R injury model was constructed. HK-2 cells were incubated with puerarin (1 uM and 10 uM) before the H/R model. Immunohistochemistry, immunocytochemistry, and Western blot analysis were used to detect the protein associated with apoptosis and endoplasmic reticulum stress.

RESULTS

Puerarin could improve renal function and attenuate tissue structural damage after renal I/R. Meanwhile, puerarin alleviated apoptosis and endoplasmic reticulum stress by decreasing expression levels of specific biomarkers such as caspase-3, GRP78, CHOP, and p-elF2α/ elF2α in animals and HK-2 cells. The up-regulated expression of Nrf2 and HO-1 protein after puerarin treatment indicated that the Nrf2/HO-1 signaling pathway might mediate the protective mechanism of puerarin against renal I/R.

CONCLUSION

Our results suggest that puerarin alleviated renal ischemia/reperfusion injury by inhibiting apoptosis and endoplasmic reticulum stress via the Nrf2/HO-1 pathway and offered new insights for preventing and treating renal I/R.

摘要

目的

探讨葛根素对肾缺血/再灌注损伤的影响及其可能机制。

材料与方法

将实验小鼠每天腹腔注射葛根素(50或100毫克/千克)或等量无菌生理盐水,持续一周,构建肾缺血/再灌注损伤模型。在缺氧/复氧模型建立前,将HK-2细胞与葛根素(1微摩尔和10微摩尔)共同孵育。采用免疫组织化学、免疫细胞化学和蛋白质印迹分析检测与凋亡和内质网应激相关的蛋白质。

结果

葛根素可改善肾缺血/再灌注后的肾功能,减轻组织结构损伤。同时,葛根素通过降低动物和HK-2细胞中半胱天冬酶-3、葡萄糖调节蛋白78、C/EBP同源蛋白和磷酸化真核翻译起始因子2α/真核翻译起始因子2α等特定生物标志物的表达水平,减轻凋亡和内质网应激。葛根素处理后Nrf2和HO-1蛋白表达上调,表明Nrf2/HO-1信号通路可能介导了葛根素对肾缺血/再灌注的保护机制。

结论

我们的结果表明,葛根素通过Nrf2/HO-1途径抑制凋亡和内质网应激,减轻肾缺血/再灌注损伤,为预防和治疗肾缺血/再灌注提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c317/11756738/c1622ca8efb8/ijbms-28-187-g001.jpg

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