Korkach Iu P, Rudyk O V, Kotsiuruba A V, Prysiazhna O D, Sahach V F
Fiziol Zh (1994). 2007;53(5):22-8.
This study evaluated generation of O2*- and NO in heart mitochondria isolated from 9-week old streptozotocin (STZ)-induced diabetic rats and the effect of ecdysterone treatment on these parameters. Mitochondria isolated from 9-week old placebo-treated rats were used as control. Several parameters were evaluated: O2*- production, the levels of stable NO metabolites nitrate, nitrite and total nitrosothiols, the level of bilirubine (as marker of CO generation), inducible (iNOS) and constitutive (nNOS) mtNOS, NADH- dependent nitrate reductase (NR) and inducible arginase II (AII) activity. We observed that diabetes was accompanied by a significant decrease in nNOS activity, nitrite, total nitrosothiols and bilirubine content while iNOS, NR and AII activity, as well as O2*- generation was increased in heart mitochondria. Ecdysterone treatment normalized the levels of stable NO metabolites, ability to generate superoxide, iNOS and nNOS activity, but not bilirubine level, NR and AII activity. These results suggest that ecdysterone treatment attenuates diabetes-induced mitochondrial alterations protecting against oxidative and nitrosative stresses. Thus, ecdysterone therapy, besides its well known importance in the maintenance of glycemic control, may help to protect against mitochondrial dysfunction associated to several age-related disorders.
本研究评估了从9周龄链脲佐菌素（STZ）诱导的糖尿病大鼠分离的心脏线粒体中O2*-和NO的生成，以及蜕皮甾酮处理对这些参数的影响。从9周龄接受安慰剂处理的大鼠分离的线粒体用作对照。评估了几个参数：O2*-生成、稳定的NO代谢产物硝酸盐、亚硝酸盐和总亚硝基硫醇的水平、胆红素水平（作为CO生成的标志物）、诱导型（iNOS）和组成型（nNOS）线粒体一氧化氮合酶、NADH依赖性硝酸还原酶（NR）和诱导型精氨酸酶II（AII）活性。我们观察到，糖尿病伴随着nNOS活性、亚硝酸盐、总亚硝基硫醇和胆红素含量的显著降低，而心脏线粒体中的iNOS、NR和AII活性以及O2*-生成增加。蜕皮甾酮处理使稳定的NO代谢产物水平、产生超氧化物的能力、iNOS和nNOS活性恢复正常，但胆红素水平、NR和AII活性未恢复正常。这些结果表明，蜕皮甾酮处理可减轻糖尿病诱导的线粒体改变，保护机体免受氧化应激和亚硝化应激。因此，蜕皮甾酮疗法除了在维持血糖控制方面具有众所周知的重要性外，可能有助于预防与几种年龄相关疾病相关的线粒体功能障碍。
