Abstract:

Objective

To explore the protective effect and mechanism of epigallocatechin gallate（EGCG） on acute kidney injury （AKI） in mice.

Methods

An AKI model of renal unilateral ischemiareperfusion injury was established in mice.Thirty C57BL/6J mice aged 8-10 weeks were randomly divided into sham operation group， AKI mode solvent group （intraperitoneal injection of equal volume saline for 3 consecutive days）， AKI mode EGCG low-dose group （intraperitoneal injection of 6.25 mg/kg EGCG for 3 consecutive days），AKI mode EGCG medium-dose group （intraperitoneal injection of 12.5 mg/kg EGCG for 3 consecutive days），and AKI mode EGCG high-dose group （intraperitoneal injection of 25 mg/kg EGCG for 3 consecutive days）， with 6 mice in each group.After 3 days of the intervention， samples were taken to measure serum creatinine （Scr） and blood urea nitrogen （BUN） to evaluate renal function， while periodic acid-Schiff staining of renal tissue was used to evaluate the degree of renal tubular injury.Western blot and PCR were used to detect the expression levels of renal injury markers， cell cycle-related senescence markers， and senescence-associated secretory phenotypes.Observation of cellular senescence was performed with β-galactosidase staining in renal tissues.

Results

Compared with the sham operation group， the AKI mode solvent group showed significantly elevated levels of Scr and BUN， as well as more severe renal tubular injury （all P ＜0.05）.Compared with the AKI mode solvent group， the AKI mode EGCG medium-dose group exhibited significantly reduced levels of Scr and BUN， and reduced degree of renal tubular injury （all P ＜0.05）.In contrast， both the AKI mode EGCG low-dose group and the AKI mode EGCG high-dose group did not show any improvement in the above indicators.Additionally， compared with the AKI mode solvent group， the AKI mode EGCG medium-dose group also displayed significantly downregulated expression levels of renal injury markers， cell cycle-related senescence markers， and senescence-associated secretory phenotypes （all P ＜0.05）， and the positive area of β-galactosidase staining was also reduced apparently （P ＜0.05）.

Conclusion

Medium dose （12.5 mg/kg） of EGCG could effectively alleviate the renal unilateral ischemia-reperfusion AKI in mice， and its protective mechanism might be related to the inhibition of the renal tubular senescence.

Key words: Epigallocatechin gallate, Acute kidney injury, Cellular senescence, Senescenceassociated secretory phenotypes