梓葛冻干粉针抗脑缺血“神经血管单元”多细胞凋亡的机制  

Anti-apoptotic mechanisms of lyophilized powder of catapol and puerarin against brain ischemia damage on neurovascular unit cells

作　　者：薛强[1] 王红玉[1] 孙文威 杨盛[1] 魏述永[2] 徐晓玉[1,3,4] 

机构地区：[1]西南大学药学院.中医药学院,重庆400715 [2]西南大学荣昌校区,重庆402460 [3]西南大学中药研究所,重庆400715 [4]重庆市药效评价工程技术研究中心,重庆400715

出　　处：《中华中医药杂志》2016年第5期1716-1722,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81473549;No.31402237);国家科技重大新药创制专项(No.2014ZX09304-306-04);教育部博士学科点专项基金项目(博导类No.20110182110012);教育部中央高校教师基本科研专项(No.XDJK2014D023);重庆市卫生局中医药科技重大项目(No.2010[60]2010-1-4)~~

摘　　要：目的:研究梓葛冻干粉针(C-P)抗脑缺血"神经血管单元"(NVU)多细胞凋亡的机制。方法:通过线栓法制作的脑缺血再灌注(I/R)损伤大鼠模型,氧糖剥夺再灌注(OGD/R)损伤的体外NVU模型,采用形态学和免疫学方法,研究C-P抗缺血NVU多细胞凋亡的机制。结果:在I/R损伤模型大鼠实验中,49.00、24.50、12.25μg/m L的C-P均能显著抑制Cleaved Caspase-3、Caspase-3和Bax蛋白表达(P<0.01,P<0.05),降低缺血区神经元、微血管内皮细胞和星形胶质细胞凋亡率(P<0.01),减少梗死灶体积百分比(P<0.01),提高大鼠神经行为学得分(P<0.01)。在OGD/R损伤NVU体外模型实验中,49.00、24.50μg/m L的C-P均能显著抑制Cleaved Caspase-3、Caspase-3和Bax蛋白表达(P<0.01),降低神经元、微血管内皮细胞和星形胶质细胞的凋亡率(P<0.01),增加神经元轴突长度以及星形胶质细胞和微血管内皮细胞的存活数量(P<0.01)。结论:C-P可同时抑制神经元、微血管内皮细胞和星形胶质细胞凋亡,促进其存活,对NVU具有整体保护作用,从而减少缺血区梗死灶体积,起到改善大鼠神经行为学功能的效果。Objective： To observe the anti-apoptotic mechanisms of lyophilized powder of catalpol and puerarin（C-P） against brain ischemia damage on neurovascular unit cells. Methods： In ischemic/reperfusion（I/R） rats and in oxygen and glucose deprivation/reperfusion（OGD/R） damaged NVU models, the anti-apoptotic mechanisms of C-P against brain ischemia damage on neurovascular unit cells was investigated. Results： In I/R rats, the C-P at all of the doses（49.0, 24.5, 12.25μg/m L） significantly inhibited the expression of Cleaved caspase-3, Caspase-3 and Bax（P〈0.01, P〈0.05）, and decreased the apoptosis rates of neurons, brain microvascular endothelial cells（BMECs） and astrocytes in ischemic regions（P〈0.01）. It also significantly reduced the infarct volume（P〈0.01）, and ameliorated neurological deficiency in I/R rats（P〈0.01）. Further, in OGD/R-damaged NVU, 49μg/m L C-P have same effect on inhibiting the expression of Cleaved caspase-3, Caspase-3 and Bax（P〈0.01）, and decreasing the apoptosis rates of the three types of cells（P〈0.01）. Additionally, it significantly increased the neuronal axon length, and the number of astrocytes and BMECs（P〈0.01）. Conclusion： The C-P could protect NVU cells from brain ischemia damage through inhibiting the apoptosis of neurons, BMECs and astrocytes simultaneously, thus ameliorating the neurological deficiency of I/R rats with the decreasing of cerebral infarct volume.

关 键 词：梓葛冻干粉针 脑神经血管单元 缺血性脑中风 氧糖剥夺再灌注 神经保护 凋亡 

分 类 号：R285.5[医药卫生—中药学]