灯盏乙素苷元对缺氧缺血性脑损伤新生大鼠PI_3K/Akt传导通路的影响

Effect of scutellarein on the signal pathway of PI_3K/AKT in neonatal rats with hypoxia-ischemia brain damage

【目的】研究灯盏乙素苷元对缺氧缺血性脑损伤(hypoxia-ischemia brain damage,HIBD)新生大鼠脑组织磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3 kinase/protein kinase B,PI_3K/Akt)传导通路的影响。【方法】将新生7日龄Wistar大鼠制备成HIBD动物模型,随机分为假手术组、缺氧缺血模型组、灯盏乙素苷元高、中、低剂量组、PI_3K抑制剂+灯盏乙素苷元高剂量组。处死动物后,HE染色观察脑组织病理学改变,干湿重法检测脑含水量,Western blotting技术检测脑组织中磷酸化蛋白激酶B(phosphorylated Akt,p-Akt)、核因子κB(nuclear factorκB,NF-κB)、B细胞淋巴瘤-2(B cell lymphoma-2,Bcl-2)蛋白表达。【结果】缺氧缺血模型组大鼠脑含水量(74.19±0.58)%较假手术组(67.28±0.25)%显著增加(P<0.01),病理学损伤明显,脑组织Bcl-2蛋白表达减少(P<0.01),NF-κB表达增加(P<0.01);与HIBD模型组比较,灯盏乙素苷元组大鼠脑组织含水量降低(P<0.05),光镜下脑组织缺氧缺血性损伤明显改善,脑组织p-Akt和Bcl-2表达增强(P<0.05),NF-κB表达显著降低(P<0.05);PI_3K抑制剂可抑制灯盏乙素苷元的上述作用。【结论】灯盏乙素苷元可能通过PI_3K/Akt信号传导通路,抑制神经细胞凋亡和炎症反应,从而发挥脑保护作用。

【Objective】To explore the effect of scutellarein on the phosphatidylinositol 3 kinase/protein kinase B（PI_3K/AKT） signaling pathway in neonatal rats with hypoxia-ischemia brain damage（HIBD）.【Methods】The 7-day-old neonatal Wistar rats were used to make the model of HIBD. The rats were randomly divided into six groups： sham operation group, hypoxic-ischemic brain damage group（HIBD）,scutellarein-treated groups with three different doses, and PI_3K inhibitor＋high-dose-of-scutellarein group. The morphological change of brain tissues was observed via H.E staining. The water content of brain was detected by dry and wet weight method. The protein expressions of phosphorylated Akt（p-AKT）, nuclear factor κB（NF-κB） and B cell lymphoma-2（Bcl-2） were detected by Western blotting.【Results】Compared with the sham operation group（67.28±0.25）%, the brain water content in the HIBD group（74.19±0.58）% increased（P〈0.01）,The rats in the HIBD group showed obvious pathological injury and the protein expression of Bcl-2 decreased while the protein expression of NF-κB increased（P0.01）. Compared with the HIBD group, scutellarein could decrease brain water content（P0.05）, increase the protein expressions of p-Akt and Bcl-2 and decrease the protein expression of NF-κB（P0.05）. Hypoxic-ischemic injury was improved in brain tissue under light microscope. The PI_3K inhibitor could reverse the above results. 【Conclusion】 Scutellarein may inhibit neuronal apoptosis and inflammation through the PI_3K/Akt signaling pathway and play a role in protecting the brain.