Therapeutic Effect Of Osthole On Renovascular Hypertension-Induced Cardiac Hypertrophy And Its Possible Mechanisms In Rats

Aim: To investigate the therapeutic effect of osthole on renovascular hypertension-induced cardiac hypertrophy in rats and its possible mechanisms.Methods: The rat model of cardiac hypertrophy was established by two kidney-oneclip, followed by oral administration of osthole10mg/kg and20mg/kg for4weeks. At theend of the experiment, the blood pressure, heart weight index, myocardial superoxidedismutase （SOD）, glutathione peroxidase （GSH-P_x） and malondialdehyde （MDA） contents,blood glucose and free fatty acids （FFA） in serum and myocardium were measured.Pathomorphological changes in myocardial tissue were examined under a light microscope.The mRNA expressions of peroxisome proliferator-activated receptor （PPAR）_α, PPAR_γ,carnitine palmitoyltransferase-1（CPT-1）, diacylglycerol acyltransferase （DGAT）, glucosetransporter-4（GLUT-4） and transforming growth factor-β₁（TGF-β₁） in myocardial tissuewere determined by reverse transcription-polymerase chain reaction （RT-PCR） method.Results: The blood pressure, heart weight index, MDA in myocardium, and FFA inserum and myocardium were lowered in the osthole-treated groups, especially in theosthole20mg/kg/d group （P<0.05or P<0.01）, while the myocardial SOD and GSH-Pxcontents were obviously increased （P<0.01）, and the blood glucose was also reversed（P<0.01）. Importantly, the histological evaluation demonstrated that osthole could improvethe cardiomyocyte hypertrophy. The RT-PCR results showed that osthole couldsignificantly up-regulate the mRNA expressions of PPARα, PPAR_γ and CPT-1inhypertrophic myocardial tissue （P<0.05or P<0.01）, and down-regulate the mRNAexpressions of DGAT, GLUT-4and TGF-β₁in myocardial tissue （P<0.01）.Conclusion: Osthole was effective in alleviating renovascular hypertension-inducedcardiac hypertrophy in rats, and the main mechanisms might be related to its improvementof myocardial energy metabolism, inhibition of myocardial TGF-β₁expression, and reduction of myocardial oxidative stress via increment of myocardial PPAR_α/γ geneexpressions.