摘要
目的观察胰岛素样生长因子-1(IGF-1)对幼年大鼠癫痫持续状态(SE)的保护作用及其相关作用机制的初步探讨。方法选择出生21 d的幼年SD大鼠,采用戊四唑(PTZ)制作SE模型,于海马区立体定位注射IGF-1,分为生理盐水对照组(NS)、癫痫模型组(PTZ组)、癫痫模型IGF-1处理组(PTZ+IGF-1组);于造模后第2天,用ELISA检测神经元特异性烯醇化酶(NSE)含量,RT-PCR(real-time PCR)检测海马中的IGF-1表达情况;Western blot检测海马中p-ERK和p-Akt表达情况;于造模后第5天,HE染色观察海马的病理变化,以及免疫荧光染色标记增殖细胞数(Brd U)和神经干细胞数(Nestin)。结果 SE后第2天,PTZ组血清中NSE含量最高,极显著高于NS组和PTZ+IGF-1组(P<0.01);PTZ组海马IGF-1基因表达极显著高于NS组(P<0.01);PTZ组海马p-ERK和p-Akt的蛋白的表达量明显高于NS组(P<0.05),同时PTZ+IGF-1组p-ERK和p-Akt的蛋白的表达量明显高于PTZ组(P<0.01);SE后PTZ组海马相比其他两组出现了明显的炎性细胞浸润,细胞结构紊乱等变化;SE后PTZ组海马Brd U阳性细胞数及Nestin阳性细胞数都明显高于NS组(P<0.05),同时PTZ+IGF-1组Brd U阳性细胞数及Nestin阳性细胞数都极明显高于PTZ组(P<0.01)。结论 IGF-1对幼年大鼠SE后具有明显的神经保护作用,并可能通过MEK/ERK和PI3K/Akt两条通路发挥作用。
[Objective] To observe the protective effect of IGF-1 on rats with status epilepticus （SE） and its re- lated mechanism. [Methods] Postnatal day 21 SD rats were intraperitoneally injected of pentetrazole （PTZ） to estab- lish the SE models. Stereotactic injection of IGF-1 was performed in the hippocampus. All rats were randomly re- spectively assigned to three groups： saline control group （NS）, epilepsy model group （PTZ group）, epilepsy model with IGF-1 treatment group （PTZ ＋ IGF-1 group）. Two days after modeling, neuron-specific enolase （NSE） content was detected by ELISA, IGF-1 expression in hippocampus was detected by RT-PCR, p-ERK and p-Akt expressions in hippocampus were detected by Western blot. Five days after modeling, HE staining was used to observe pathological changes in the hippocampus. Immunofluorescence staining was used to label the proliferation ceils （BrdU） and neural stem cells （Nestin）. [ Results ] Two days after modeling, the levels of NSE in serum was the highest of PTZ group, which significantly higher than NS group and PTZ ＋ IGF-1 group （P 〈 0.01）; IGF-1 gene expression in hippocampus of FIE group was significantly higher than that of the NS group （P 〈 0.01）; the expression of p-ERK and p-Akt pro- tein in hippocampus of PTZ group was significantly higher than that of the NS group （P 〈 0.05）, while the expression of p-ERK and p-Akt protein in hippocampus of PTZ ＋ IGF-1 group was significantly higher than that of PTZ group （P 〈 0.01）; After SE, PTZ group appeared obvious inflammatory cell infiltration and cell structural disorder in hip-pocampus compared with the other groups; after SE, BrdU-positive cells and nestin-positive cells in hippocampus of PTZ group were significantly higher than those of the NS group （P 〈 0.05）, while BrdU-positive cells and nestin- positive cells in hippocampus of PTZ ＋ IGF-1 group were significantly higher than those of PTZ group （P 〈 0.01）. [Conclusions] IGF-1 has significant neuroprotec
出处
《中国现代医学杂志》
CAS
北大核心
2015年第22期28-33,共6页
China Journal of Modern Medicine
