Probucol treatment reverses antioxidant and functional deficit in diabetic cardiomyopathy
Probucol treatment reverses antioxidant and functional deficit in diabetic cardiomyopathy
复制标题
DOI：
10.1007/bf00240060
复制
发表时间：
1996-07-01
影响因子：
4.3
通讯作者：
Singal, PK
中科院分区：
文献类型：
--
作者：
Kaul, N;SiveskiIliskovic, N;Singal, PK
早些时候我们报道过，在诱发糖尿病后进行普罗布考治疗可以预防与糖尿病相关的心肌抗氧化剂以及 8 周时的功能变化。在这项研究中，我们检查了普罗布考在逆转糖尿病引起的心肌变化中的功效。通过单次注射链脲佐菌素（65 mg/kg，静脉注射）使大鼠患上糖尿病。诱导糖尿病 4 周后，一组动物每隔一天接受普罗布考（10 毫克/千克，腹腔注射）治疗，普罗布考是一种已知的具有抗氧化特性的降脂剂。第 8 周时，糖尿病组的左心室 (LVSP) 和主动脉收缩压 (ASP) 显着下降。这些动物的心脏显示硫代巴比妥酸反应物质（TBARS）增加，表明脂质过氧化增加。这伴随着心肌抗氧化酶活性、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSHPx）的降低。糖尿病组心肌过氧化氢酶活性较高。在糖尿病+普罗布考组中，LVSP 和 ASP 均显示出显着恢复。这还伴随着 SOD 和 GSHPx 活性的改善，以及过氧化氢酶活性的进一步增加。该组的 TBARS 水平降低。这些数据提供的证据表明，糖尿病性心肌病与抗氧化缺陷有关，而抗氧化缺陷可以通过普罗布考治疗来逆转。普罗布考改善心脏功能可能是由于心脏中抗氧化剂的恢复。
Earlier we reported that probucol treatment subsequent to the induction of diabetes can prevent diabetes-associated changes in myocardial antioxidants as well as function at 8 weeks. In this study, we examined the efficacy of probucol in the reversal of diabetes induced myocardial changes. Rats were made diabetic with a single injection of streptozotocin (65 mg/kg, i.v.). After 4 weeks of induction of diabetes, a group of animals was treated on alternate days with probucol (10 mg/kg i.p.), a known lipid lowering agent with antioxidant properties. At 8 weeks, there was a significant drop in the left ventricle (LVSP) and aortic systolic pressures (ASP) in the diabetic group. Hearts from these animals showed an increase in the thiobarbituric acid reacting substances (TBARS), indicating increased lipid peroxidation. This was accompanied by a decrease in the myocardial antioxidant enzymes activities, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). Myocardial catalase activity in the diabetic group was higher. In the diabetic + probucol group both LVSP and ASP showed significant recovery. This was also accompanied by an improvement in SOD and GSHPx activities and there was further increase in the catalase activity. Levels of the TBARS were decreased in this group. These data provide evidence that diabetic cardiomyopathy is associated with an antioxidant deficit which can be reversed with probucol treatment. Improved cardiac function with probucol may be due to the recovery of antioxidants in the heart.