PolyphyllinⅠ alleviates myocardial ischemia/reperfusion injury via nuclear factor-κB signal pathway / 中华危重病急救医学

ABSTRACT

Objective To investigate the protective effect of PolyphyllinⅠ(PPI) on myocardial ischemia/reperfusion (I/R) injury in rats and its mechanism. Methods The 6-month-old Sprague-Dawley (SD) rats were divided into sham operation group (Sham group), I/R model group, and low, medium, high dose PPI groups according to the random number table method, with 10 in each group. The rat myocardial I/R model was prepared by ligating the left anterior descending branch of the coronary artery by 30 minutes and reperfusion by 120 minutes. Sham group was exposure to open chest without ligation. Low, medium, high dose PPI groups were injected with PPI 75, 150, 300 mg·kg-1·d-1 in front of the film for 4 weeks; dimethyl sulfoxide (DMSO) was gastric infused in the I/R model group. After the end of reperfusion, the myocardial infarction area (IA) was determined by triphenyltetrazole (TTC) and Evans blue (EB) staining;the apoptosis of myocardial cells was detected by TdT-mediated dUTP nick end labeling stain (TUNEL); the expressions of apoptosis related protein (Bax, Bcl-2), and cytoplasmic and nucleus expressions of P65 in nuclear factor-κB (NF-κB) signal pathway were detected by Western Blot. Results Compared with the Sham group, the myocardial IA was significantly increased in the I/R model group, the apoptosis rate of myocardial cells was significantly increased, the expression of Bcl-2 was significantly decreased, and the expression of Bax was significantly increased, and the intranuclear transfer of P65 was significantly increased. Compared with the I/R model group, low, medium and high dose PPI pretreatment could significantly reduce the myocardial IA [(21.6±0.9)%, (14.3±1.6)%, (15.0±0.8)% vs. (29.6±1.4)%], the apoptosis rate of myocardial cells was significantly decreased [(38.6±1.9)%, (24.3±2.6)%, (26.3±2.8)% vs. (56.8±2.4)%], the protein expression of Bcl-2 was significantly increased, while the protein expression of Bax was significantly decreased (Bcl-2/GAPDH 0.24±0.07, 0.36±0.02, 0.34±0.09 vs. 0.13±0.04; Bax/GAPDH 0.39±0.10, 0.21±0.08, 0.23±0.06 vs. 0.53±0.12); and P65 nuclear transfer was significantly decreased after middle and high dose PPI pretreatment [nuclear P65/Histone 3 0.49±0.09, 0.51±0.06 vs. 0.83±0.11; cytoplasmic P65/GAPDH 0.31±0.03, 0.30±0.05 vs. 0.22±0.07], with statistically significant differences (all P < 0.05). However, there was no significant difference in each index between the medium and high dose PPI groups (all P > 0.05). Conclusion PPI alleviates myocardial I/R injury in rats via NF-κB signal pathway, and the PPI effect of 150 mg·kg-1·d-1 is most especially significant.