4-苯基丁酸对糖尿病大鼠的心脏保护作用

Protective effects of 4-phenyl butyrate acid on the heart function of diabetic rats

目的观察4-苯基丁酸(4-PBA)对糖尿病大鼠心脏功能的影响并初步探讨其机制。方法♂Sprague-Dawley(SD)大鼠随机分成3组:对照组、糖尿病组和糖尿病+4-PBA组。单次腹腔注射链脲佐菌素(60 mg·kg-1)诱发大鼠糖尿病,在1型糖尿病模型制备成功后第5周开始每天给予大鼠4-PBA(1g·kg-1)灌胃,连续治疗20周。实验结束后,经右颈总动脉插管检测大鼠大动脉和左心室血流动力学变化,同时收集血清和心脏,比色法检测血糖,血清和心肌组织中超氧化物歧化酶(SOD)和一氧化氮合酶(NOS)活性,丙二醛(MDA)和一氧化氮(NO)含量。结果 4-PBA治疗对糖尿病大鼠血糖、体重和心脏重量无明显影响,但可改善糖尿病大鼠血流动力学,表现为大动脉收缩压和舒张压、心率、左心室收缩压和左心室内压最大上升和下降速率(±dp/dt)的轻度升高,左心室舒张压的轻度降低和舒张时程的缩短(P>0.05),左心室弛缓时间明显缩短(P<0.05)。4-PBA治疗尚可明显升高糖尿病大鼠血清和心肌组织SOD和NOS活力以及NO含量,并降低MDA含量(P<0.05)。结论 4-PBA治疗对糖尿病大鼠心脏有潜在保护作用,这一作用是通过改善糖尿病大鼠血流动力学和明显缓解其心脏舒张功能障碍而实现,并与其抑制动物体内氧化应激和促进心肌NO生成有关。

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＆#183;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＆#183;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（ ＆#177; dp/dt） in di-abetic rats. It also slightly decreased diastolic pressure of left ventricular, shortened diastolic duration of left ventricular （ P ＆gt; 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.