Matsunami Tokio, Sato Yukita, Sato Takuya, Ariga Satomi, Shimomura Toshiko, Yukawa Masayoshi
Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa 252-8510, Japan.
Int J Clin Exp Pathol. 2009 Nov 30;3(2):177-88.
Diabetes mellitus (DM) causes not only hyperglycemia but oxidative stress, resulting mainly enhanced production of mitochondrial reactive oxygen species (ROS). Hyperbaric oxygen (HBO) treatments are applied various diseases including diabetic patients with unhealing foot ulcers, however, and also increases the formation of ROS. Recently, it has been reported that oxidative stress worsens many pathological conditions including DM and obesity suggesting possible changes in regulation of genes associated with the oxidative stress, however, effects of HBO which could induce ROS on the gene expressions of oxidative stress parameters in DM animals are unknown. The purpose of this study is to investigate the effect of HBO exposure on the gene expression of three important antioxidant enzymes, cytosolic superoxide dismutase (Cu-Zn SOD), cytosolic glutathione peroxidase (GPx-1), and catalase (CAT) in DM rats, respectively. We used streptozotocin-induced DM model rats and examined both mRNA expressions and the activities of these antioxidant enzymes in the liver, skeletal muscle, and pancreas. The mRNA expressions of Cu-Zn SOD and CAT decreased significantly (p < 0.001), and GPx increased significantly (p < 0.001) in all the studied organs of DM rats under HBO exposure compared to those from DM-induced rats not exposed to HBO. Similarly, activities of these three enzymes changed in accordance with the mRNA levels. These results suggested that DM induction and HBO exposure might synergistically affect antioxidant enzymes, resulting increase of oxidative stress state. Thus, HBO exposure seems to be an excellent model system for investigating oxidative stress.
糖尿病（DM）不仅会导致高血糖，还会引发氧化应激，主要表现为线粒体活性氧（ROS）生成增加。然而，高压氧（HBO）治疗已应用于包括患有难愈合足部溃疡的糖尿病患者在内的多种疾病，但其同样会增加ROS的形成。最近，有报道称氧化应激会使包括糖尿病和肥胖症在内的许多病理状况恶化，这表明与氧化应激相关的基因调控可能发生了变化，然而，能诱导ROS的HBO对糖尿病动物氧化应激参数基因表达的影响尚不清楚。本研究的目的是分别研究HBO暴露对糖尿病大鼠三种重要抗氧化酶，即胞质超氧化物歧化酶（Cu-Zn SOD）、胞质谷胱甘肽过氧化物酶（GPx-1）和过氧化氢酶（CAT）基因表达的影响。我们使用链脲佐菌素诱导的糖尿病模型大鼠，检测了肝脏、骨骼肌和胰腺中这些抗氧化酶的mRNA表达和活性。与未暴露于HBO的糖尿病诱导大鼠相比，暴露于HBO的糖尿病大鼠所有研究器官中Cu-Zn SOD和CAT的mRNA表达显著降低（p < 0.001），而GPx显著增加（p < 0.001）。同样，这三种酶的活性也随mRNA水平而变化。这些结果表明，糖尿病诱导和HBO暴露可能会协同影响抗氧化酶，导致氧化应激状态增加。因此，HBO暴露似乎是研究氧化应激的一个极佳模型系统。
