Conclusions
PA regulates different mechanisms at different concentrations to improve myocardial injury, and high dose is the best. This experiment provides a theoretical basis for the development of new clinical drugs for cardiovascular disease.
Methods
In vivo, SHR rats were treated with or without PA (15, 30, 45 mg/kg) for 3 weeks (12 per group). In vitro, H9c2 cells were treated with PA (1, 5, 10 μM) for 24 h, and then stimulated with H2O2 (300 μM) for 4 h. Molecular mechanisms were explored through cardiac pathology, cardiac function and biochemical markers.
Objective
Clarify the protective mechanism of PA on myocardial injury in SHR rats.Materials and
Results
In vivo, PA (15, 30, 45 mg/kg) reduced CVF from 14.8 ± 1.62 to 9.94 ± 1.56, 8.6 ± 1.33, 8.14 ± 1.45%; increased the LVEF relative level from 0.8 ± 0.06 to 0.83 ± 0.04, 0.86 ± 0.05, 0.9 ± 0.04. All three doses can improve the cardiac pathological structure and function (LVEDD, LVESD, LVFS, heart index, NT-proBNP, CKMB, SBP); however, 45 mg/kg works best. But different doses show different molecular mechanisms. PA (15 mg/kg) improves RAAS system (REN, ACE), inflammation (ET-1, IL-1β) and MAPK pathway (p-ERK/ERK, p-JNK/JNK) better. PA (45 mg/kg) improves oxidative stress (SOD, NOX1) and TGF-β pathway (Smad3) better. In vitro, PA improved cell viability, oxidative stress (SOD, NOX1) and Smad3 protein expression.