Zhang Fan, Ru Neng, Shang Zheng-Hui, Chen Jian-Feng, Yan Chao, Li Yun, Liang Jie
Department of Orthopedics, The First People's Hospital of Yichang, China Three Gorges University, Yichang, Hubei 443000, P.R. China.
Exp Ther Med. 2017 Nov;14(5):4878-4886. doi: 10.3892/etm.2017.5166. Epub 2017 Sep 21.
Daidzein (DZ) has a broad spectrum of biological activities, including antioxidant, anti-inflammatory and anticancer as well as cardio- and hepatoprotective properties. The present study was designed to elucidate the in-depth mechanism underlying the neuroprotective efficacy of DZ against spinal cord ischemic/reperfusion injury (SCII) in a rat model by comparison with the standard neuroprotective agent methylprednisolone (MP). A total of 48 rats were divided into four groups of twelve rats in each (n=12). In sham-operated group (Control) group, rats received only saline (Fogarty catheter was inserted without balloon inflation), whereas rats in the SCII induction group (SCII) were subjected to SCII insult by insertion of a Fogarty balloon catheter, which was inflated in the descending thoracic aorta to cause an occlusion. A proportion of rats was treated with DZ (20 mg/kg; DZ+SCII group) or MP (50 mg/kg; MP+SCII group) for seven days prior to and after SCII. The locomotor function (neurological activity) and antioxidant levels (superoxide dismutase and catalase) levels were significantly improved upon treatment with DZ and MP in comparison with those in the SCII group. A concomitant decline in edema, inflammatory markers (myeloperoxidase, tumor necrosis factor-α and nuclear factor κB p65), the apoptotic marker caspase-3 and the number of cells with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was also observed in the DZ and MP groups. The protein levels of phosphoinositide-3 kinase (PI3K), the phosphorylated Akt/Akt ratio and B-cell lymphoma 2 (Bcl-2) were substantially downregulated, while Bcl-2-associated X protein levels were upregulated SCII insult group, which was inhibited by treatment with DZ. To conclude, pre-treatment with DZ significantly improved the neurological function by upregulating PI3K/Akt signaling and thereby considerably attenuating the inflammatory response and apoptosis, thus maintaining the neuronal count in an SCII-induced rat model.
大豆苷元（DZ）具有广泛的生物活性，包括抗氧化、抗炎、抗癌以及心脏和肝脏保护特性。本研究旨在通过与标准神经保护剂甲基强的松龙（MP）比较，阐明DZ对大鼠脊髓缺血/再灌注损伤（SCII）神经保护作用的深入机制。总共48只大鼠被分为四组，每组12只（n = 12）。在假手术组（对照组），大鼠仅接受生理盐水（插入Fogarty导管但不充盈球囊），而SCII诱导组（SCII组）的大鼠通过插入Fogarty球囊导管遭受SCII损伤，该导管在降主动脉中充盈以造成阻塞。一部分大鼠在SCII前后7天用DZ（20 mg/kg；DZ + SCII组）或MP（50 mg/kg；MP + SCII组）治疗。与SCII组相比，用DZ和MP治疗后，运动功能（神经活动）和抗氧化水平（超氧化物歧化酶和过氧化氢酶）显著改善。在DZ和MP组中还观察到水肿、炎症标志物（髓过氧化物酶、肿瘤坏死因子-α和核因子κB p65）、凋亡标志物半胱天冬酶-3以及末端脱氧核苷酸转移酶介导的dUTP缺口末端标记的细胞数量同时下降。磷脂酰肌醇-3激酶（PI3K）、磷酸化Akt/Akt比值和B细胞淋巴瘤2（Bcl-2）的蛋白水平显著下调，而Bcl-2相关X蛋白水平在SCII损伤组中上调，用DZ治疗可抑制这种上调。总之，在SCII诱导的大鼠模型中，DZ预处理通过上调PI3K/Akt信号通路显著改善神经功能，从而大大减轻炎症反应和细胞凋亡，维持神经元数量。
