干细胞因子对糖尿病小鼠皮层神经元凋亡的保护作用

SCF protects the cortical neuron from apoptotic cell death in diabetic mice

目的探讨干细胞因子对糖尿病所致神经元凋亡的干预效应及其可能机制。方法成年雄性C57小鼠27只,随机分为正常对照组、糖尿病组、糖尿病干细胞因子组,每组9只。用链脲佐菌素建立糖尿病小鼠模型,TUNEL染色反映大脑神经元的凋亡情况,Western blot检测BCL-2、BAX、CASPASE3及P-ERK/ERK蛋白的表达。结果与对照组相比,糖尿病小鼠大脑皮层神经元凋亡数量增加且有活性的CASPASE3表达升高,应用干细胞因子干预后,上述情况可以得到有效的改善。糖尿病小鼠大脑皮层内的BCL-2、BAX均较正常组明显升高,应用干细胞因子后可抑制BAX的表达而对BCL-2无明显影响;相应的BCL-2/BAX比值在正常组和糖尿病组之间无显著性差异存在,但干细胞因子的应用能明显升高其表达。糖尿病小鼠P-ERK表达水平明显降低,应用干细胞因子后可有效增加ERK的磷酸化甚至超过正常水平。结论干细胞因子可能通过增加ERK的磷酸化而影响BCL-2/BAX的表达发挥对糖尿病神经元的抗凋亡作用。

Objective To investigate the role of SCF on neuronal apoptosis induced by diabetes and its possible mechanism. Methods Twenty-seven male C57 mice were randomly divided into control group, diabetes group, and diabetes plus stem cell factor（SCF） group. The diabetic mice were induced by streptozotocin. TUNEL staining was used to assess neuronal apoptosis and western blot were used to detect the protein level of BCL-2, BAX, CASPASE 3 and P-ERK/ERK. Results Compared with the controls, the number of apoptotic neuron death and the protein levels of active CASPASE 3 were significantly increased in the cortex of diabetic mice. Treatment with SCF significantly reduced apoptotic neuron death and attenuated the increased in protein levels of active CASPASE 3 in the cortex of diabetic mice. The levels of BCL-2 and BAX were significantly increased in the diabetic animals compared to the controls. Treatment with SCF could significantly attenuated the increase in the expression of BAX but could not affect the level of BCL-2 in the cortex of diabetic mice. P- ERK was significantly decreased in the diabete group but not in dibete plus SCF group. Conclusions SCF can protect against diabete-induced apoptotic neuron death through increasing the phosphorylation of ERK and influencing the expression of BCL-2/BAX.