胶质细胞源性神经营养因子对大鼠局灶脑缺血损伤的保护作用

Protective effects of glial derived neurotrophic factor on focal cerebral ischemia in rats.

目的 从胶质细胞源性神经营养因子(GDNF)对大鼠局灶脑缺血梗死灶、半胱氨酸蛋白酶(Caspase-3)表达、细胞凋亡等方面的影响,研究其对大鼠局灶脑缺血的作用及其机制。方法 健康雄性Wistar大鼠120只,随机分为GDNF组和生理盐水组,每组又分为假手术组、缺血oh、3h、6h、24h组,采用大脑中动脉线栓模型,于栓塞同时大鼠脑室内分别给予GDNF和生理盐水5μL。检测脑梗死体积百分比、Caspase-3的表达、细胞凋亡等改变。结果 GDNF组脑梗死体积比明显小于生理盐水组;神经元损伤明显轻于生理盐水组,特别是海马区神经元在GDNF组无明显损伤;GDNF组(Caspase-3表达和TUNEL染色阳性细胞数明显少于生理盐水组。结论 GDNF对大鼠局灶脑缺血有保护作用,抑制Caspase-3的表达和细胞凋亡是其保护机制之一。

Objective By studying the influence of glial derived neurotrophic factor (GDNF) on the focal cerebral ischemia, the expression of Caspase-3 and neuronal apoptosis, to investigate the role of GDNF in cerebral ischemia and its possible mechanism .Methods 120 healthy male Wistar rats were divied randomly into GDNF group and saline group. Each group were divided further into shamed operation subgroup and 0h, 3h, 6 h and 24 h subgroup according to the time exposed to ischemia. The model of middle cerebral artery occlusion was performed with intraluminal filament occlusion. At the same time of occlusion, 5μl of GDNF and saline was injected respectively into the cerebral ventricle of the rats. The infarction volume percent, expression of Caspase-3 and neuronal apoptosis were observed. Results The cerebral infarction volume of GDNF group was significantly smaller than those of saline group. Neuron injury of GDNF group was less serious than saline group, and it's noteworthy that hippocampus neuron even bore no obvious injury. A significant decrease of the number of Caspase-3 and TUNEL staining positive neuron was detected also in GDNF group. Conclusions GDNF does have protective effects on focal cerebral ischemia. Inhibiting the expression of Caspase-3 and neuronal apoptosis may be one of the possible mechanisms of the event.