Tetramethylpyrazine alleviates acute kidney injury by inhibiting NLRP3/HIF‑1α and apoptosis

Sun,Wangnan; Li,Aiqun; Wang,Zhiqiang; Sun,Xuhong; Dong,Menghua; Qi,Fu; Wang,Lin; Zhang,Yueheng; Du,Pengchao

doi:10.3892/mmr.2020.11378

Tetramethylpyrazine alleviates acute kidney injury by inhibiting NLRP3/HIF‑1α and apoptosis

Authors:
- Wangnan Sun
- Aiqun Li
- Zhiqiang Wang
- Xuhong Sun
- Menghua Dong
- Fu Qi
- Lin Wang
- Yueheng Zhang
- Pengchao Du
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Affiliations: Institute of Pathology and Pathophysiology, School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Emergency Department, Yantai Affiliated Hospital, Binzhou Medical University, Yantai, Shandong 264003, P.R. China , Department of Geriatrics, the Second Hospital of Shandong University, Jinan, Shandong 264001, P.R. China
Published online on: July 28, 2020 https://doi.org/10.3892/mmr.2020.11378
Pages: 2655-2664
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the protective effect and underlying mechanism of tetramethylpyrazine (TMP) on renal ischemia reperfusion injury (RIRI) in rats, which refers to the injury caused by the restoration of blood supply and reperfusion of the kidney after a period of ischemia. Sprague‑Dawley rats were randomly divided into a Sham group, renal ischemia‑reperfusion (I/R) group and TMP group. TMP hydrochloride (40 mg/kg, 6 h intervals) was given via intraperitoneal injection immediately after reperfusion in the TMP group, after 24 h the kidney tissues were taken for follow‑up experiments. Pathological changes in the kidney tissues were observed by periodic acid‑Schiff staining. Renal function was assessed by measuring levels of serum creatinine and blood urea nitrogen, and inflammatory cytokines tumor necrosis factor (TNF)‑α and interleukin (IL)‑6. Renal cell apoptosis was detected by TUNEL‑DAPI double staining, mRNA and protein changes were analyzed by reverse transcription‑quantitative PCR and western blotting. Cell viability was measured using a CCK‑8 assay. It was found that the renal tissues of the sham operation group were notably abnormal, and the renal tissues of the I/R group were damaged, while the renal tissues of the TMP group were less damaged compared with those of the I/R group. Compared with the I/R group, the serum creatinine and blood urea nitrogen levels in the TMP group were low (all P<0.05), levels of inflammatory cytokines TNF‑α and IL‑6 decreased, the apoptotic rate was low (all P<0.05), and the relative expression levels of nucleotide‑oligomerization domain‑like receptor 3 (NLRP3) protein and mRNA in renal tissues were low (all P<0.05). The expression levels of hypoxia‑inducible factor 1‑α and NLRP3 increased after oxygen and glucose deprivation (OGD), and reduced after treatment with OGD and TMP (all P<0.05). It was concluded that TMP can reduce renal injury and improve renal function in RIRI rats, and its mechanism may be related to the reduction of NLRP3 expression in renal tissues.

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