大豆异黄酮基于RhoA/ROCK2信号通路改善MCAO大鼠神经功能损伤

目的:探讨大豆异黄酮对脑缺血再灌注大鼠RhoA/ROCK2信号通路介导的氧化应激反应和神经元凋亡的影响。方法:60只SD大鼠随机分为3组,对照组、模型组、大豆异黄酮组。连续给药7天后,给药剂量200 mg/kg。应用中动脉栓塞再灌注模型致大鼠缺血损伤。24 h后评价大鼠神经功能,TTC染色检测脑梗死体积,试剂盒检测脑中氧化因子含量,免疫组化检测神经元损伤,Western Blotting检测RhoA/ROCK2相关蛋白含量。结果:与对照组比较,模型组大鼠神经功能评分降低(P0.05),脑梗死体积增加(P0.05),氧化因子含量增加(P0.05),神经元凋亡显著(P0.05),RhoA/ROCK2蛋白表达增加(P0.05)。与模型组相比,大豆异黄酮升高了大鼠神经功能评分(P0.05),减少的脑梗死体积(P0.05),降低脑中氧化因子含量(P0.05),抑制了神经元凋亡(P0.05),抑制了RhoA/ROCK2蛋白表达(P0.05)。结论:大豆异黄酮可以缓解脑缺血再灌注损伤介导的氧化应激及细胞凋亡,进而减轻神经功能障碍,其机制可能与抑制RhoA/ROCK2信号通路相关。

Soybean Isoflavones Improve Neurological Damage in MCAO Rats Based on RhoA/ROCK2 Signaling Pathway

ABSTRACT Objective: To investigate the effect of soybean isoflavones on oxidative stress and neuronal apoptosis in rats with cerebral ischemia-reperfusion through RhoA / ROCK2 signaling pathway. Methods: Sixty SD rats were randomly divided into three groups: Control group, Model group and Soybean isoflavone group. After continuous administration of Soybean isoflavone for 7 days, the cerebral ischemia / reperfusion operations were performed for neurologic deficit in rats. 24 hours later, the neurological function of rats were evaluated. The cerebral infarct size was assessed through TTC staining. The content of oxidative factor in the brain was detected through elisa kit. And neuronal damage was detected through Immunohistochemistry. Results: Compared with Control group, the neurological function score of Model group significantly decreased (P<0.05), the cerebral infarct size increased (P<0.05), the content of oxidizing factor increased (P<0.05), and neuronal apoptosis was increased(P<0.05), furthermore, RhoA/ROCK2 protein expression raised (P<0.05). Compared with Model group, soy isoflavones improved the neurological function(P<0.05), reduced cerebral infarction volume (P<0.05), lower down the content of oxidative factors in the brain(P<0.05), and inhibited neuronal apoptosis(P<0.05) and decreased RhoA/ROCK2 protein expression(P<0.05). Conclusion: Soybean isoflavone can alleviate oxidative factors and neuronal apoptosis induced by cerebral ischemia/reperfusion, and further reverse neurological dysfunction which is related to the inhibition of RhoA/ROCK2 signaling pathway.