【摘要】：目的探討抑制c-Jun氨基末端激酶(JNK)/核轉(zhuǎn)錄因子FOXO3a信號(hào)通路對(duì)缺氧缺血性腦損傷(HIBD)新生大鼠神經(jīng)元凋亡的保護(hù)作用機(jī)制。方法將64只7日齡Sprague-Dawley大鼠隨機(jī)分為假手術(shù)組、缺氧缺血(HI)組、二甲基亞砜(DMSO)溶劑組和JNK特異性抑制劑AS601245干預(yù)組(JNK抑制劑組)。各組分別在建模后24 h處死動(dòng)物取大腦皮層,應(yīng)用Western blot法定量檢測(cè)JNK、p-JNK、FOXO3a、胞核FOXO3a、胞漿FOXO3a,以及促凋亡蛋白Bim及CC3的表達(dá)水平;應(yīng)用TUNEL染色法檢測(cè)神經(jīng)細(xì)胞凋亡情況。結(jié)果與假手術(shù)組相比,HI后24 h,p-JNK蛋白水平增高(P0.01);胞核FOXO3a蛋白水平增高,胞漿FOXO3a蛋白水平降低(P0.01);Bim及CC3表達(dá)水平增高(P0.01)。與HI組及DMSO溶劑組相比,JNK抑制劑組p-JNK蛋白水平降低(P0.01);胞核FOXO3a蛋白水平降低,胞漿FOXO3a蛋白水平增高(P0.01);Bim及CC3表達(dá)水平降低(P0.01)。JNK抑制劑組的TUNEL染色陽(yáng)性細(xì)胞表達(dá)較HI組及DMSO溶劑組減少(P0.01)。結(jié)論新生大鼠HIBD時(shí),JNK發(fā)生磷酸化,活性增高;抑制JNK活性可抑制FOXO3a核轉(zhuǎn)位,下調(diào)促凋亡蛋白Bim及CC3表達(dá),減少神經(jīng)細(xì)胞凋亡。
[Abstract]:Objective to investigate the protective mechanism of inhibition of c-Jun amino-terminal kinase (JNK) / nuclear transcription factor FOXO3a signaling pathway on neuronal apoptosis in neonatal (HIBD) rats with hypoxic-ischemic brain injury. Methods Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into sham-operation group, hypoxic-ischemic (HI) group, dimethyl sulfoxide (DMSO) solvent group and AS601245 intervention group (JNK inhibitor group). All the animals were killed 24 hours after modeling. The expression levels of FOXO3a, cytoplasm FOXO3a, and apoptosis-promoting proteins Bim and CC3 in the nucleus of JNK,p-JNK,FOXO3a, were detected by Western blot assay. Apoptosis of nerve cells was detected by TUNEL staining. Results compared with the sham-operated group, the level of p-JNK protein increased at 24 h after HI (P0.01), the level of nuclear FOXO3a protein increased, and the level of cytoplasmic FOXO3a protein decreased (P0.01); Bim and CC3 expression level increased (P0.01). Compared with the HI group and the DMSO solvent group, the p-JNK protein level in the JNK inhibitor group decreased (P0.01), the FOXO3a protein level in the nucleus decreased and the FOXO3a protein level in the cytoplasm increased (P0.01). The expression of Bim and CC3 decreased (P0.01). JNK inhibitor group, compared with HI group and DMSO group (P0.01). Conclusion during HIBD, JNK is phosphorylated and its activity is increased, inhibition of JNK activity can inhibit FOXO3a nuclear translocation, down-regulate the expression of Bim and CC3, and decrease neuronal apoptosis.
【作者單位】： 四川大學(xué)華西第二醫(yī)院兒科/出生缺陷與相關(guān)婦兒疾病教育部重點(diǎn)實(shí)驗(yàn)室;
【基金】：國(guó)家自然科學(xué)基金(81000262) 四川省衛(wèi)生和計(jì)劃生育委員會(huì)科研課題(16PJ240);四川省衛(wèi)生和計(jì)劃生育委員會(huì)資助項(xiàng)目(140045)
【分類號(hào)】：R742

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