脓毒症大鼠模型脑胰岛素生长因子1表达的变化及影响

Changes of insulin-like growth factor-1 expression and its effects on brain of rat sepsis model

目的探讨脓毒症大鼠模型胰岛素生长因子1(IGF-1)表达的变化及影响。方法采用盲肠结扎穿孔法(CLP)制作脓毒症大鼠模型,应用免疫荧光染色观察皮层IGF-1阳性细胞,western blot法检测IGF-1和caspase-3蛋白表达,TUNEL染色观察脑神经元凋亡。在脓毒症模型基础上,给予侧脑室定位注射IGF-1或生理盐水,相同方法检测caspase-3蛋白表达及脑神经元凋亡。结果与假手术组相比,脓毒症组大鼠皮层IGF-1阳性细胞数明显减少,caspase-3表达增高,IGF-1表达减低,神经元凋亡增加(均P<0.05)。侧脑室注射IGF-1后,caspase-3表达和神经元凋亡较假手术组无明显变化;而侧脑室给予生理盐水大鼠caspase-3表达和神经元凋亡与脓毒症组相似。结论脓毒症大鼠的脑皮层IGF-1表达明显减低,细胞凋亡增多。给予外源性IGF-1后,细胞凋亡减少。提示IGF-1可能通过抑制caspase-3的上调对脓毒症大鼠起到脑保护作用。

Objective To explore the change of insulin-like growth factor-1（ IGF-1） expression and its effects on cerebral cortex of rat sepsis model .Methods The rat model of sepsis was established by cecal ligation and puncture （ CLP ） .The IGF-1 positive cells were observed by immunofluorescent staining .IGF-1 and caspase-3 expression was determined by Western blot . TUNEL staining was used to assess neuron apoptosis .Then septic rats were treated with IGF-1 or saline by lateral ventricle injection .The expression of caspase-3 was evaluated by western blot . Neuron apoptosis was assessed by TUNEL staining .Results Compared with the sham-operated group, IGF-1 positive cells in cerebral cortex in the sepsis group decreased obviously .Besides, IGF-1 expression decreased , caspase-3 expression and neuron apoptosis increased （all P〈0.05）. When IGF-1 was given , caspase-3 expression and cell apoptosis was similar to the sham-operated group, while in the saline-treated group, the results were similar to the sepsis group .Conclusion During sepsis , IGF-1 expression in rat cerebral cortex obviously decreased and neuron apoptosis increased.After treated with exogenous IGF-1, cell apoptosis decreased .These findings suggested that IGF-1 may protect rat brain from sepsis by inhibiting the up-regulation of caspase-3.