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目的:观察糖尿病脑病大鼠海马组织氧化应激水平及脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达,初步探讨小檗碱治疗糖尿病脑病的机制。方法:除空白组给予普通饲料外,其余大鼠高糖高脂饲料喂养60d,腹腔注射40mg/kg链脲佐菌素(Streptozocin,STZ)制备糖尿病模型,模型成功后随机分为模型组、小檗碱低(50mg/kg)、中(100mg/kg)、高(200mg/kg)剂量组,罗格列酮组(5mg/kg)。给药30d后处死大鼠取血,检测血糖,部分动物取海马组织测定过氧化氢酶(CAT)、过氧化脂质(LPO)、还原型谷胱甘肽(GSH)。其余动物取脑进行BDNF免疫组化染色。结果:较空白组,模型大鼠体重明显降低,血糖显著升高(P<0.05,P<0.01),小檗碱中、高剂量及罗格列酮可显著降低模型大鼠血糖(P<0.01,P<0.05),升高CAT活性、GSH水平(P<0.01),降低LPO水平(P<0.01),提高海马CA1区BDNF的表达。结论:糖尿病脑病与氧化应激水平及海马组织BDNF表达降低相关,小檗碱可通过降血糖,抗氧化,增强神经营养因子表达而发挥脑保护作用。
OBJECTIVE: To observe the oxidative stress and the expression of brain-derived neurotrophic factor (BDNF) in hippocampus of diabetic encephalopathy rats and to explore the mechanism of berberine in the treatment of diabetic encephalopathy. Methods: The rats in the blank group were fed with normal diet, the other rats were fed with high-fat and high-fat diet for 60 days, and the diabetic rats were injected intraperitoneally with 40 mg / kg Streptozocin (STZ). The models were randomly divided into model group Berberine low (50mg / kg), medium (100mg / kg), high (200mg / kg) dose group and rosiglitazone group (5mg / kg). Rats were sacrificed 30 days after administration to take blood, blood glucose was measured, and some animals were taken to measure catalase (CAT), lipid peroxidation (LPO) and reduced glutathione (GSH) in hippocampus. The remaining animals were brains for BDNF immunohistochemical staining. Results Compared with the blank group, the body weight of the model rats decreased significantly and the blood glucose level increased significantly (P <0.05, P <0.01). The berberine medium and high dose and rosiglitazone could significantly reduce the blood glucose of model rats , P <0.05), increased CAT activity, GSH level (P <0.01), decreased LPO level (P <0.01), and increased BDNF expression in CA1 hippocampus. Conclusion: The diabetic encephalopathy is related to the level of oxidative stress and the decrease of BDNF expression in the hippocampus. Berberine can exert cerebral protective effect by lowering blood glucose, antioxidation and enhancing the expression of neurotrophic factor.