Biología Celular, Histología y Embriología. Facultad de Ciencias Médicas, INICSA CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina.
Geriatric Center "San Ricardo Pampuri", Villa Carlos Paz and Gerontology Committee, Argentine Society of Diabetes, Córdoba, Argentina.
Lipids Health Dis. 2019 Feb 8;18(1):43. doi: 10.1186/s12944-018-0938-7.
Diabetic encephalopathy is a chronic complications of diabetes mellitus that affects the central nervous system. We evaluated the effect of ω3 and ω6 polyunsaturated fatty acids (PUFAs) supplementation plus the antioxidant agent nordihydroguaiaretic acid (NDGA) on the etiopathology of diabetic encephalopathy in eSS rats, a spontaneous model of type 2 diabetes.
One hundred twenty spontaneous diabetic eSS male rats and 38 non-diabetic Wistar, used as healthy control, received monthly by intraperitoneal route, ω3 or ω6 PUFA (6.25 mg/kg) alone or plus NDGA (1.19 mg/kg) for 12 months. Diabetic rats had a worse performance in behavioural Hole-Board test. Histopathological analysis confirmed lesions in diabetic rats brain tissues. We also detected low expression of synaptophysin, a protein linked to release of neurotransmitters, by immunohistochemically techniques in eSS rats brain. Biochemical and histopathological studies of brain were performed at 12th month. Biochemical analysis showed altered parameters related to metabolism. High levels of markers of oxidative stress and inflammation were detected in plasma and brain tissues. Data were analysed by ANOVA test and paired t test was used by comparison of measurements of the same parameter at different times.
The data obtained in this work showed that behavioural, biochemical and morphological alterations observed in eSS rats are compatible with previously reported indices in diabetic encephalopathy and are associated with increased glucolipotoxicity, chronic low-grade inflammation and oxidative stress burden. Experimental treatments assayed modulated the values of studied parameters.
The treatments tested with ω3 or ω3 plus NDGA showed improvement in the values of the studied parameters in eSS diabetic rats. These observations may form the basis to help in prevent and manage the diabetic encephalopathy.
糖尿病性脑病是一种影响中枢神经系统的糖尿病慢性并发症。我们评估了ω3 和 ω6 多不饱和脂肪酸(PUFAs)补充剂加抗氧化剂 NDGA(去甲二氢愈创木酸)对 eSS 大鼠糖尿病性脑病发病机制的影响,eSS 大鼠是 2 型糖尿病的自发性模型。
120 只自发性糖尿病 eSS 雄性大鼠和 38 只非糖尿病 Wistar 大鼠作为健康对照,每月通过腹腔途径给予 ω3 或 ω6 PUFAs(6.25mg/kg)单独或加 NDGA(1.19mg/kg),共 12 个月。糖尿病大鼠在行为性洞板测试中表现更差。组织病理学分析证实了糖尿病大鼠脑组织的病变。我们还通过免疫组织化学技术检测到 eSS 大鼠脑组织中突触素的低表达,突触素是一种与神经递质释放相关的蛋白质。在第 12 个月进行了大脑的生化和组织病理学研究。生化分析显示与代谢相关的参数发生改变。在血浆和脑组织中检测到氧化应激和炎症标志物的水平升高。数据采用方差分析进行分析,采用配对 t 检验比较不同时间同一参数的测量值。
本工作获得的数据表明,eSS 大鼠观察到的行为、生化和形态改变与先前报道的糖尿病性脑病中的指数一致,并且与葡萄糖脂毒性增加、慢性低度炎症和氧化应激负担有关。所测试的实验治疗方法调节了所研究参数的值。
ω3 或 ω3 加 NDGA 的治疗方法改善了 eSS 糖尿病大鼠研究参数的值。这些观察结果可能为预防和治疗糖尿病性脑病提供依据。