Protective effects of 4-phenyl butyrate acid on the heart function of diabetic rats / 中国药理学通报

ABSTRACT

Aim Tostudytheeffectof4-phenlybuty-rate acid(4-PBA) on the heart function of diabetic rats and to explore its underlying mechanism. Methods MaleSprague-Dawley(SD)ratsweredividedintothree groups randomly ( 1 ) control rats;( 2 ) diabetic rats;(3) 4-PBA treated diabetic rats. Type 1 diabetic mod-el was induced by single intraperitoneal injection of strepotozotocin (60 mg·kg-1 ) . After five weeks dia-betic model was established, diabetic rats were treated with 4-PBA by P. O at the dose of 1 g·kg-1 per day for 20 weeks. At the end of the experiment, hemody-namics of the left ventricle and main artery were detec-ted through right carotid artery cannulation in rats. The level of blood glucose, the activity of superoxide dis-mutase( SOD) and nitric oxide synthetase ( NOS) and the content of malondialdehyde ( MDA ) and nitric ox-ide( NO) of serum and myocardial tissue in rats were measuredbycolorimetry.Results Thetreatmentof4-PBA had no effect on blood glucose, the weight of body and heart, but slightly increased systolic and diastolic pressure of artery, heart rate, systolic pressure of left ventricular, maximum increase rate and minimum de-crease rate of left ventricular pressure( ± dp/dt) in di-abetic rats. It also slightly decreased diastolic pressure of left ventricular, shortened diastolic duration of left ventricular ( P > 0. 05 ) . Moreover, it significantly shortened relaxation time of left ventricular in diabetic rats (P<0. 05). In addition, the treatment of 4-PBA obviously enhanced the activity of SOD and NOS, NO content, and reduced the content of MDA in serum and heartofdiabeticrats(P<0.05).Conclusion 4-PBA has a potential protective effect on heart function in diabetic rats, which is achieved by ameliorating he-modynamics and significantly improving diastolic dys-function in diabetic rats. The underlying mechanism may be related to the inhibition of oxidative stress and promoting the genesis of NO in myocardial tissue.