Naringin pretreatment alleviating myocardial cell hypoxia/reoxygenation injury by suppressing endoplasmic reticulum stress-induced apoptosis / 中国药理学通报

ABSTRACT

Aim: To study the effect of naringin (Nar) on endoplasmic reticulum stress (ERS) -induced apoptosis in H9c2 myocardial cell hypoxia/reoxygenation (H/R) injury and its molecular mechanism. Methods: H9c2 cells were cultured in vitro and randomly classified into five groups normal control (group C), H/R group, H/R with Nar 10 mg · L-1 (group L), H/R with Nar20 mg · L-1 (group M) and H/R with Nar40 mg · L-1 (group H). Myocardial cells were normally cultured until the end of the experiment in group C. The myocardial cells were treated by hypoxia for 4 h before reoxygenation for 24 h in group H/R. The myocardial cells were cultured with Nar(10, 20, 40 mg · L-1) respectively 6 h before hypoxia, and after 6 h they were treated by hypoxia for 4 h before reoxygenation for 24 h in group L, group M and group H. The survival rate of cells was determined by MTT method after experiment. The apoptosis of cardiomyocytes was detected by TUNEL. CCAAT/enhancer-binding protein-homologous protein(CHOP), activating transcription factor-4(ATF4), eukaryotic initiation factor 2α (eIF2α), p-eIF2α, double-stranded RNA like endoplasmic reticulum kinase (PERK) and p-PERK were all assessed by Western blot. Results: Compared with group C, H9c2 cell viability decreased, induced apoptosis and the protein expression of CHOP, ATF4, peIF2α/eIF2α and p-PERK/PERK in group H/R were significantly increased (P < 0. 05). Compared with group H/R, H9c2 cell viability increased, the apoptosis and the protein expression of CHOP, ATF4, peIF2α/eIF2α and p-PERK/PERK were reduced in group L, group M and group H. Of the three groups, group M and group H showed the most significant effect (P < 0. 05). Conclusions: The Nar pretreatment can reduce myocardial cell apoptosis caused by H/R injury, suggesting that Nar can help to relieve the ERS-associated apoptosis through the PERK-eIF2α-ATF4- CHOP pathway.