Mondal Papia, Trigun Surendra Kumar
Biochemistry Section, Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
Evid Based Complement Alternat Med. 2015;2015:535013. doi: 10.1155/2015/535013. Epub 2015 Aug 27.
Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells. Bacopa monnieri (BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE.
肝性脑病（HE）的特征是慢性肝功能衰竭（CLF）期间小脑功能受损，它涉及脑细胞中N-甲基-D-天冬氨酸受体（NMDAR）的过度激活。水飞蓟宾提取物是一种已知的神经保护剂。本文评估水飞蓟宾提取物是否能够调节慢性肝功能衰竭（CLF）大鼠小脑内的两种NMDAR亚基（NR2A和NR2B）及其下游介质。CLF大鼠通过腹腔注射50mg/kg体重的硫代乙酰胺（TAA）14天诱导产生，在第8至14天，TAA组大鼠口服200mg/kg体重的水飞蓟宾提取物。已知NR2A具有神经保护作用，而NR2B在NMDAR激活过程中会诱导神经元死亡。已知神经元型一氧化氮合酶（nNOS）凋亡途径介导NMDAR导致的兴奋性毒性。发现CLF大鼠小脑中NR2A水平显著降低，同时NR2B增加。这与nNOS表达显著增强、一氧化氮水平升高以及Bcl2/Bax比率降低一致。此外，用水飞蓟宾提取物治疗可逆转NR2A/NR2B比率，并使这些大鼠小脑中nNOS凋亡因子的水平恢复正常。研究结果表明，水飞蓟宾提取物可调节NR2A和NR2B的表达，以预防与肝性脑病相关的神经化学改变。
