胰岛素样生长因子-1对痴呆模型大鼠额叶、海马Caspase-3 P20活性片段及Bcl-2蛋白表达的影响

Effects of insulin-like growth factor-1 on the expression of caspase-3 P20 and Bcl-2 in frontal lobe and hippocampus of dementia model rats

目的探讨胰岛素样生长因子-1(IGF-1)对痴呆模型大鼠额叶、海马caspase-3 P20活性片段及Bcl-2蛋白表达的影响。方法本研究采用切断成年Wistar大鼠双侧穹隆海马伞,建立隔-海马胆碱能系统损害的痴呆模型。分为正常对照组、假手术组、痴呆组、小剂量胰岛素样生长因子-1(IGF-1)组、大剂量IGF-1组。痴呆模型制备1d后开始侧脑室给药,连续21d。正常对照组不给予任何处置。利用免疫组织化学染色结合图像分析方法观察各组大鼠额叶、海马胆碱能神经元caspase-3 P20活性片段、Bcl-2蛋白的表达,并进行光密度值(IOD)测定。结果小剂量IGF-1组和大剂量IGF-1组与痴呆组相比,caspase-3 P20阳性神经元IOD值明显降低,具有显著差异(P<0.001)。小剂量IGF-1组与大剂量IGF-1组比较,caspase-3 P20阳性神经元IOD值明显降低,具有显著性差异(P<0.05或P<0.01)。小剂量IGF-1组和大剂量IGF-1组与痴呆组相比,额叶、海马Bcl-2阳性神经元明显增多,IOD值明显增加,具有显著差异(P<0.001)。小剂量IGF-1组与大剂量IGF-1组比较,Bcl-2阳性细胞增多,IOD值明显增高,差异显著(P<0.05或P<0.01)。结论 IGF-1能够通过抑制caspase-3的活化并增加Bcl-2的表达量,减少细胞凋亡。

Objective To study the effects of insulin-like growth factor-1（IGF-1） on the expression of caspase-3 P20 and Bcl-2 in frontal lobe and hippocampus of dementia model rats.Methods We established the dementia rat models by transecting bilateral fornix-fimbria and divided them into five groups：normal control group,sham group,dementia group,low dose IGF-1 group and large dose IGF-1group.Dementia model rats received IGF-1（low dose IGF-1 group and large dose IGF-1group） or saline（sham group and dementia group） by cerebroventricully infusion for 21 days after the operation.The normal control group accept no treatment.The expression of caspase-3 P20 and Bcl-2 in frontal lobe and hippocampus of rats in each group were observed,which optical density value（IOD） were determined by immunohistochemistry and image analysis system.Results Compared with the dementia group,caspase-3 P20 intensity of cell positive response in low dose IGF-1 group and large dose IGF-1 group was decreased,student＇s t-test reveals significant difference in cell IOD value（P0.001）.Comparing with large dose IGF-1group,low dose IGF-1 group＇s Caspase-3 P20 IOD value was decreased obviously,with significant difference（P0.05 or P0.01）.Compared with the dementia group,Bcl-2 IOD value of low dose IGF-1 group and large dose IGF-1group was decreased obviously,which was determined by student＇s t-test revealed significant difference（P0.001）.Student＇s t-test suggested that the Bcl-2 IOD value increased significantly in low dose IGF-1 group compared with large dose IGF-1group.It indicated that Low dose IGF-1 group was better than large dose IGF-1group on the expression of Bcl-2（P0.05 or P0.01）.Conclusions The experimental results manifest that IGF-1 can decrease the expression of caspase-3 P20 and increase the expression of Bcl-2 in frontal lobe and hippocampus of rats to depress cell apoptosis in dementia model rats.