载脂蛋白E基因敲除及高脂饮食小鼠海马CA1和CA3区神经元内IP3及IP3R-1表达的变化

Apolipoprotein E gene knock-out and high-fat diet on IP3 and IP3R-1 expression in neurons of mice hippocampal CA_1 and CA_3

目的观察载脂蛋白E(ApoE)基因敲除(KO)及高脂饮食小鼠海马CA1和CA3区神经元内三磷酸肌醇(IP3)和三磷酸肌醇受体-Ⅰ(IP3R-1)表达的变化。方法将30只C57BL/6J小鼠分为对照组(C组)、ApoE KO组(KO组)、ApoE KO高脂饮食组(KO-HF组)。小鼠造模成功后称重;取血检测血脂;取小鼠脑组织分别进行HE染色、免疫组织化学染色和计算机图像分析。结果与C组比较,KO、KO-HF组体重、总胆固醇、甘油三酯及低密度脂蛋白胆固醇含量明显升高(P<0.05)。HE染色观察到,KO和KO-HF组小鼠海马锥体细胞排列较松散,胞体较小。与C组比较,KO组小鼠海马CA1和CA3区神经元内IP3和IP3R-1平均光密度值均降低,KO-HF组小鼠海马CA1和CA3区神经元内IP3和IP3R-1平均光密度值均降低明显(P<0.05)。结论 ApoE KO及高脂饮食可导致小鼠海马CA1和CA3区神经元内IP3和IP3R-1表达降低,这两种蛋白可能参与了ApoE异常,由此引发阿尔茨海默病的病理发生发展过程。

Objective To observe the change of IP3 and IP3R-1′s expression in neurons of mice′s hippocampal CA1 and CA3,which had been treated by Apolipoprotein E gene knock-out（ApoE KO） and high-fat diet.Methods 30 C57BL/6J mice were divided into 3 groups： the control group（C group）,ApoE KO group（KO group）,ApoE KO high-fat diet group（KO-HF group）.After mice model established,weight and plasma lipid of these mice were measured.The brain tissues of the mice were observed by HE staining,immunohistochemistry staining,and computer image analysis.Results The weight,total cholesterol,triglyceride,low-density lipoprotein cholesterol of the KO and KO-HF groups were all higher than those in the control group（P〈0.05）.The H-E staining showed that,in the KO and KO-HF groups,the pyramidal cell layers ranged sparse and cell body were relatively small.Compared with C group,The average optical density of IP3 and IP3R-1 in neurons of hippocampal CA1 and CA3 in the KO group reduced.The average optical density in the KO-HF group reduced obviously（P〈0.05）.Conclusion ApoE KO and high-fat diet can decrease the expression level of IP3 and IP3 R-1 in neurons of hippocampal CA1 and CA3.These two proteins（IP3 and IP3R-1） might take participate in the pathologic process in Alzheimer disease which caused by the abnormal ApoE.