Relationship of GRK5 and oxidative stress in sustained βAR-stimulated cardiac hypertrophy / 国际生物医学工程杂志

ABSTRACT

Objective To explore the role of GRK5 in sustained β adrenergic receptor (βAR)-stimulated increased levels of oxidative stress.Methods Male SD rats (180-200 g) were separated into 4 groups according to the random principal control group (CTRL), control with NAC supplement group (CTRL+NAC), ISO treated group (ISO), and ISO treated with NAC supplement group (ISO+NAC), with 6 rats in each group.ISO group was treated by method of intraperitoneal injection for 3 mg/(kg· d).CTRL rats received same volume of physiological saline by same method, while NAC was treated by supplement in drinking water for 15 g/L per day.After 2 weeks of treatment, BP, heart mass index (HMI), histology changes, expression of NOX4 and GRK5 of myocardium was examined.Results HMI of ISO rats was significantly higher than that of the CTRL group [(3.99±0.10 vs 3.31±0.13) mg/g, P＜0.05], and the cardio-myocyte cross-sectional area of ISO group was also significantly increased compared with CTRL group [(11 117.00±387.57 vs 4572.23±176.39) μm, P＜O.05].ISO+NAC significantly reduced the ISO-induced increases of heart weight index (3.56±0.12 mg/g, vs ISO, P＜0.05) and myocyte cross-sectional area (6160.33±141.44 μm2, vs ISO,P＜0.05).The immunohistochemistry results showed that the expression of myocardial NOX4 of ISO group was significantly higher than that of CTRL group [(10.59±1.61 vs 4.35±1.65), P＜0.05], and NAC reduced the ISO induced NOX4 expression increase [(4.67±1.25 vs 10.59±1.61), P＜0.05].Western Blot and immunohistochemistry were used to detect the protein expression of myocardial GRK5.Both results showed that there were no significant differences between ISO and CTRL, ISO+NAC and ISO group (P＞0.05).RT-qPCR detected no significant differences of myocardial GRK5 mRNA expression between ISO and CTRL, ISO+NAC and ISO groups (P＞0.05).Arterial blood pressure showed no significant difference among the 4 groups of rats (P＞0.05).No significant differences were found between rats from CTRL+NAC and CTRL group.Conclusions In the mechanism of sustained βAR-stimulated cardiac hypertrophy, GRK5 may not participate the regulation of hypertrophy-induced factor, and this process needs to be proved in further study.