Mechanistic study on resveratrol alleviating renal injury in rats with uric acid nephropathy by inhibiting the PERK/eIF2α pathway

CHEN Yanhua; ZHANG Jibo; LONG Li; YU Jianfeng; XU Min; LIU Hao

doi:10.6039/j.issn.1001-0408.2026.20.09

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Mechanistic study on resveratrol alleviating renal injury in rats with uric acid nephropathy by inhibiting the PERK/eIF2α pathway

更新时间：2026-10-29

- Mechanistic study on resveratrol alleviating renal injury in rats with uric acid nephropathy by inhibiting the PERK/eIF2α pathway
- ZHONGGUO YAOFANG Vol. 37, Issue 20, Pages: 2679-2684(2026)
- 作者机构：
  
  1.湖北省妇幼保健院中西医结合科，武汉　430070
  2.湖北省第三人民医院中西医结合肾病风湿科，武汉　430033
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.20.09
  CLC： R692.5;R965
- Received：29 May 2026，
  
  Revised：2026-09-30，
  
  Accepted：08 October 2026，
  
  Published：30 October 2026
- 稿件说明：
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陈燕华,张继波,龙利,等.白藜芦醇抑制PERK/eIF2α通路改善尿酸性肾病大鼠肾损伤的机制研究 [J].中国药房,2026,37(20):2679-2684.

CHEN Yanhua,ZHANG Jibo,LONG Li,et al.Mechanistic study on resveratrol alleviating renal injury in rats with uric acid nephropathy by inhibiting the PERK/eIF2α pathway[J].ZHONGGUO YAOFANG,2026,37(20):2679-2684.
陈燕华,张继波,龙利,等.白藜芦醇抑制PERK/eIF2α通路改善尿酸性肾病大鼠肾损伤的机制研究 [J].中国药房,2026,37(20):2679-2684. DOI： 10.6039/j.issn.1001-0408.2026.20.09.

CHEN Yanhua,ZHANG Jibo,LONG Li,et al.Mechanistic study on resveratrol alleviating renal injury in rats with uric acid nephropathy by inhibiting the PERK/eIF2α pathway[J].ZHONGGUO YAOFANG,2026,37(20):2679-2684. DOI： 10.6039/j.issn.1001-0408.2026.20.09.

摘要

目的

探讨白藜芦醇通过抑制蛋白激酶R样内质网激酶（PERK）/真核翻译起始因子2α（eIF2α）通路改善尿酸性肾病（UAN）大鼠肾损伤的机制。

方法

采用腺嘌呤+氧嗪酸钾灌胃的方式构建UAN大鼠模型，并将其分为UAN模型组、阳性对照组（别嘌醇10 mg/kg）、白藜芦醇组（100 mg/kg）、白藜芦醇+衣霉素组（白藜芦醇100 mg/kg+PERK激活剂衣霉素1 mg/kg），另设对照组（未造模），每组6只。各组大鼠灌胃、腹腔注射相应药液和（或）生理盐水，每天1次，连续28 d。检测各组大鼠肾功能相关指标（24 h尿蛋白定量和血清中尿酸、肌酐、血尿素氮）含量、炎症相关指标[白细胞介素6（IL-6）、IL-18、肿瘤坏死因子α（TNF-α）、IL-10、核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3（NLRP3）]水平；观察其肾组织病理改变，并进行肾小管损伤评分、炎症浸润评分和系膜基质增生程度评估；检测其肾组织内中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肾损伤分子1（KIM-1）mRNA的表达水平以及PERK/eIF2α通路相关蛋白的表达情况。

结果

与对照组比较，UAN模型组大鼠肾小管损伤、炎症细胞浸润、系膜基质增生明显；其肾功能指标含量，IL-6、IL-18、TNF-α、NLRP3水平，肾小管损伤和炎症浸润评分，系膜基质增生程度，NGAL、KIM-1 mRNA的表达，PERK、eIF2α蛋白的磷酸化水平，以及活化转录因子4、C/EBP同源蛋白的表达均显著升高或上调，而IL-10水平显著降低（

＜0.05）；与UAN模型组比较，白藜芦醇组和阳性对照组大鼠上述指标均显著改善（

＜0.05）。衣霉素可显著逆转白藜芦醇对上述各定量指标的改善作用（

＜0.05）。

结论

白藜芦醇可减轻UAN大鼠肾组织炎症反应，改善肾小管损伤及肾功能；上述作用可能与抑制PERK/eIF2α通路介导的内质网应激有关。

Abstract

OBJECTIVE

To investigate the mechanism by which resveratrol improves renal injury in rats with uric acid nephropathy （UAN） through inhibition of the protein kinase R-like endoplasmic reticulum kinase （PERK）/eukaryotic translation initiation factor 2α （eIF2α） pathway.

METHODS

A UAN rat model was established via oral administration of adenine plus potassium oxonate， and the rats were divided into a UAN model group， a positive control group （allopurinol 10 mg/kg）， a resveratrol group （100 mg/kg）， and a resveratrol+tunicamycin group [resveratrol 100 mg/kg+tunicamycin （PERK activator） 1 mg/kg]. A control group （without modeling） was also established， with 6 rats in each group. Rats in each group were administered the corresponding drug solution and/or normal saline via gavage or intraperitoneal injection once daily for 28 consecutive days. The contents of renal function-related parameters （24-hour urinary total protein， and uric acid， creatinine and blood urea nitrogen in serum）， the levels of inflammation-related markers [interleukin-6 （IL-6）， IL-18， tumor necrosis factor-α （TNF-α）， IL-10， and nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）]， and pathological changes in renal tissue were determined， and the score for tubular damage， the score for inflammatory infiltration， and the degree of mesangial proliferation were assessed. The mRNA expressions of neutrophil gelatinase-associated lipocalin （NGAL） and kidney injury molecule-1 （KIM-1）， as well as the expressions of proteins associated with the PERK/eIF2α pathway， were measured in renal tissue from each group.

RESULTS

Compared with the control group， rats in the UAN model group exhibited marked tubular damage， inflammatory cell infiltration， and mesangial proliferation. The contents of renal function-related parameters， levels of IL-6， IL-18， TNF-α and NLRP3， scores for tubular damage and inflammatory infiltration， degree of mesangial proliferation， mRNA expressions of NGAL and KIM-1， and phosphorylation levels of PERK and eIF2α， as well as the expressions of activating transcription factor 4 and C/EBP homologous protein， were all significantly increased or upregulated， while IL-10 levels were significantly decreased （

＜0.05）. Compared with the UAN model group， the resveratrol group and the positive control group showed significant improvements in all of the aforementioned parameters （

＜0.05）. Tunicamycin could significantly reverse the beneficial effects of resveratrol on all quantitative parameters （

＜0.05）.

CONCLUSIONS

Resveratrol can reduce inflammatory responses in renal tissue of UAN rats， and improve tubular damage and renal function. These effects may be related to the inhibition of endoplasmic reticulum stress mediated by the PERK/eIF2α pathway.

关键词

Keywords

references

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