Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
J Chem Neuroanat. 2020 Oct;108:101803. doi: 10.1016/j.jchemneu.2020.101803. Epub 2020 May 29.
Diabetes mellitus is a multifactorial metabolic disorder that is complicated by multi-organ dysfunction including CNS. Klotho is an anti-aging protein expressed in Purkinje cells of the cerebellum. Klotho protects against the development of several neurodegenerative diseases. Simvastatin is a lipophilic statin that can enhance klotho expression.
This study was designed to investigate cerebellar structural changes in diabetes, klotho expression in the cerebellum of diabetic rats and the neuroprotective effect of simvastatin.
MATERIALS & METHODS: 24 adult albino rats were divided into 4 groups; control, simvastatin, diabetic (induced by single intraperitoneal injection of STZ 45 mg/kg) and diabetic treated by simvastatin (10 mg/kg once daily) after confirmation of diabetes. Rotarod test was performed for evaluation of motor coordination. Blood glucose and insulin levels were estimated for confirmation of diabetes. Reduced glutathione (GSH) and malonaldehyde (MDA) in cerebellar tissues were evaluated. The cerebellar samples were prepared for histological and immunohistochemical staining.
The latency time on the rotarod was reduced in diabetic rats. Cerebellar structure was disturbed in diabetic group. Oxidative stress was evidenced by increased MDA and reduced GSH. Klotho expression was downregulated and caspase-3 was increased in diabetes. Simvastatin increased the latency time. Simvastatin diminished the changes in oxidative stress markers and succeeded to ameliorate the diabetic induced cerebellar changes. Simvastatin enhanced Klotho and diminished Caspase-3 expression.
Simvastatin can ameliorate diabetic induced cerebellar changes through minimizing oxidative stress, enhancement of Klotho expression and reduction of apoptosis.
糖尿病是一种多因素代谢紊乱，可导致包括中枢神经系统在内的多器官功能障碍。Klotho 是一种在小脑浦肯野细胞中表达的抗衰老蛋白。Klotho 可预防多种神经退行性疾病的发生。辛伐他汀是一种亲脂性他汀类药物，可增强 Klotho 的表达。
本研究旨在探讨糖尿病大鼠小脑结构变化、小脑 Klotho 表达及辛伐他汀的神经保护作用。
24 只成年白化大鼠随机分为 4 组：对照组、辛伐他汀组、糖尿病组（单次腹腔注射 STZ45mg/kg 诱导）和糖尿病辛伐他汀治疗组（糖尿病确认后每日 10mg/kg 辛伐他汀腹腔注射）。旋转棒试验用于评估运动协调能力。检测血糖和胰岛素水平以确认糖尿病。评估小脑组织中的还原型谷胱甘肽（GSH）和丙二醛（MDA）。制备小脑样本进行组织学和免疫组织化学染色。
糖尿病大鼠在旋转棒上的潜伏期缩短。糖尿病组小脑结构紊乱。氧化应激表现为 MDA 增加和 GSH 减少。糖尿病时 Klotho 表达下调，Caspase-3 增加。辛伐他汀可延长潜伏期。辛伐他汀可减轻氧化应激标志物的变化，并改善糖尿病诱导的小脑变化。辛伐他汀增强了 Klotho 的表达，减少了 Caspase-3 的表达。
辛伐他汀通过减轻氧化应激、增强 Klotho 表达和减少细胞凋亡，可改善糖尿病诱导的小脑变化。
