Zhao Qipeng, Cheng Xiuli, Wang Xiaobo, Wang Jing, Zhu Yafei, Ma Xueqin
Department of Pharmacology, Ningxia Medical University, Yinchuan, People's Republic of China; Ningxia Hui Medicine Modern Engineering Research Center, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, People's Republic of China.
Department of Pharmacology, Ningxia Medical University, Yinchuan, People's Republic of China.
J Ethnopharmacol. 2016 Nov 4;192:140-147. doi: 10.1016/j.jep.2016.07.016. Epub 2016 Jul 8.
The present study is to investigate the neuroprotective effect of Mu-Xiang-You-Fang (MXYF), a classic Traditional Chinese Medicine used by Chinese minorities to treat stroke, on cerebral ischemia-reperfusion (I/R) injury and the related signaling pathways.
Male Sprague-Dawley rats were divided into 6 groups: sham group, I/R group, nimodipine and MXYF (58, 116 and 232mg/kg respectively) groups. Cerebral ischemia model was induced by middle cerebral artery occlusion for 2h followed by reperfusion for 48h. Neurological functional score was evaluated according to the method of Zea longa's score and the infarct area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 48h after reperfusion. The protein expression of cytochrome c (cyt-c), Bcl-2, Bax, caspase-9, caspase-3 and caspase-7 were analyzed by western blot and the mRNA expression of Caspase-9, Caspase-3 and Caspase-7 were determined by the reverse transcription-polymerase chain reaction.
Oral administration of MXYF (116 and 232mg/kg) significantly reduced the neurological functional score and attenuated the cerebral infarct area. Western blot analysis showed that the expression of Bcl-2 is enhanced and Bax expression is inhibited after treatment with MXYF (116 and 232mg/kg), leading to significant increase of the ratio between Bcl-2 and Bax. Furthermore, the protein expression of cyt-c, caspase-9, caspase-3 and caspase-7 was significantly inhibited while the mRNA expression of caspase-9, caspase-3 and caspase-7 but not cyt-c was markedly inhibited in the MXYF (116 and 232mg/kg) treatment groups compared with the I/R group.
The above data suggested that MXYF has potential neuroprotective activities by the regulation of apoptotic pathway, MXYF is a promising agent in treatment of stroke.
本研究旨在探讨麝香尤方(MXYF),一种中国少数民族用于治疗中风的经典中药,对脑缺血再灌注(I/R)损伤及相关信号通路的神经保护作用。
雄性Sprague-Dawley大鼠分为6组:假手术组、I/R组、尼莫地平组和MXYF组(分别为58、116和232mg/kg)。采用大脑中动脉闭塞2小时后再灌注48小时的方法建立脑缺血模型。再灌注48小时后,根据Zea longa评分法评估神经功能评分,并通过2,3,5-三苯基氯化四氮唑(TTC)染色确定梗死面积。采用蛋白质免疫印迹法分析细胞色素c(cyt-c)、Bcl-2、Bax、半胱天冬酶-9、半胱天冬酶-3和半胱天冬酶-7的蛋白表达,采用逆转录-聚合酶链反应测定半胱天冬酶-9、半胱天冬酶-3和半胱天冬酶-7的mRNA表达。
口服MXYF(116和232mg/kg)可显著降低神经功能评分,缩小脑梗死面积。蛋白质免疫印迹分析显示,MXYF(116和232mg/kg)处理后,Bcl-2表达增强,Bax表达受到抑制,导致Bcl-2与Bax的比值显著增加。此外,与I/R组相比,MXYF(116和232mg/kg)处理组中cyt-c、半胱天冬酶-9、半胱天冬酶-3和半胱天冬酶-7的蛋白表达显著受到抑制,而半胱天冬酶-9、半胱天冬酶-3和半胱天冬酶-7的mRNA表达明显受到抑制,但cyt-c的mRNA表达未受明显抑制。
上述数据表明,MXYF通过调节凋亡途径具有潜在的神经保护活性,MXYF是一种有前景的中风治疗药物。