小檗碱对糖尿病大鼠认知功能改善及对Notch1和Hes1蛋白表达的影响

Effects of Berberine on Improvement of Cognitive Function and Expressions of Notch1 and Hes1 Protein in Diabetic Rats

目的:研究小檗碱对糖尿病大鼠空间学习记忆障碍的改善作用以及糖尿病大鼠海马区神经元的凋亡影响。方法:制备STZ诱导的糖尿病大鼠模型,以60 mg/kg剂量的小檗碱治疗6周,检测其体重和空腹血糖水平,Morris水迷宫实验评价大鼠学习记忆能力;尼氏染色观察大鼠海马区病理改变; TUNEL染色检测大鼠海马神经元凋亡; Western Blot检测海马中Caspase3、Bcl-2、Notch1和Hes1蛋白的表达水平。结果:与模型组相比,小檗碱降低糖尿病大鼠血糖[(27. 53±3. 69) v. s.(26. 81±3. 07) mmol/L,P> 0. 05],但无统计学差异;小檗碱改善糖尿病大鼠空间记忆障碍(P <0. 05);小檗碱干预后,大鼠海马区神经元细胞排列紧密,细胞形态清晰,正常形态细胞明显增多;小檗碱降低海马区神经元的凋亡水平(P <0. 05),小檗碱组鼠大脑海马组织中Notch信号通路相关蛋白Hes1水平相对于模型组组均明显降低(P <0. 05)。结论:小檗碱调节海马组织中Notch1和Hes1蛋白而改善糖尿病大鼠认知功能障碍。

Objective: To study the effect of berberine on spatial learning and memory impairment in diabetic rats and reduce the damage of neurons in the hippocampus of diabetic rats. Methods: STZ induced diabetic rats models were interferred with berberin at a dose of 60 mg/kg berberine for 6 weeks. The experiments were divided into control,model and berberin groups. Body weight and learning capacity were examined through glucose oxidase assay and Morris water maze in diabetic male rats. Morphological change and apoptosis in hippocampus was observed by nissl staining and TUNEL method. The protien expressions were monitored by Western blotting assay. Results: Compared with the diabetic group,berberine can decrease the blood glucose of diabetic rats,but there was no significant difference. Berberine can enhance spatial learning and memory. After berberine intervention,hippocampus neurons cells were arranged closely. The morphologically normal cells were significantly increased and the cell viability was significantly increased. Berberine decreased hippocampal neuron apoptosis significantly( P < 0. 05) and inhibited STZ-induced abnormal activated Caspase-3 expression,down-regulated the expressions of abnormal activated Notch1 and Hes1( P <0. 05) and up-regulated the expression of Bcl-2 protein. Conclusion: Berberine can improve the spatial memory disorder of diabetic rats by reducing the apoptosis of hippocampus through Notch1/Hes1-Bcl-2.