苦参碱通过激动大麻素2型受体对脑缺血-再灌注大鼠的神经保护作用  

Neuroprotective effects of matrine by activating cannabinoid 2 receptor on focal cerebral ischemia-reperfusion injury in rats

作　　者：唐蜜[1] 董志[1] 蔡江晖[1] 饶梦琳 何锦悦[1] 

机构地区：[1]重庆医科大学药学院生化与分子药理研究室,重庆400016

出　　处：《中国新药与临床杂志》2014年第4期311-316,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金面上项目(81173066);国家科技重大专项重大新药创制(2010ZX09401-306-1-1);重庆市自然科学基金重点项目(CSTC2009BA5086)

摘　　要：目的探究苦参碱通过激动大麻素2型(CB2)受体对脑缺血-再灌注大鼠的神经保护作用。方法采用改良线栓法制作大鼠局灶性脑缺血(1.5 h)-再灌注(24 h)模型。72只雄性大鼠随机分为假手术组、模型组、苦参碱20 mg·kg-1组、苦参碱50 mg·kg-1组、选择性CB2受体拮抗剂AM630组和AM630+苦参碱50 mg·kg-1组。观察神经功能症状,检测梗死面积、脑组织形态学改变、凋亡细胞数、cleaved caspase-3及Bcl-2蛋白表达。结果与模型组相比,苦参碱20 mg·kg-1和50 mg·kg-1组大鼠神经功能显著改善,脑梗死体积缩小,病理形态学改变减轻,细胞凋亡数及cleaved caspase-3阳性细胞减少,Bcl-2阳性细胞显著增加(均P<0.05)。AM630+苦参碱50 mg·kg-1组大鼠上述改变均被AM630阻断,与苦参碱50 mg·kg-1组相比均有非常显著差异(P<0.01)。结论 CB2受体可能参与苦参碱对脑缺血-再灌注大鼠的神经保护作用。AIM To investigate the neuroprotective effect of matrine by activating cannabinoid 2 （CB2） receptor on focal cerebral ischemia-reperfusion （I/R） injury in rats. METHODS Focal cerebral I/R injury in rat was made by inserting a thread into internal carotid artery for 1.5 h and then reperfused for 24 h. Seventy-two male adult SD rats were randomly divided into sham group, I/R group, matrine 20 mg·kg^-1 and matrine 50 mg·kg^-1 groups, selective CB2 receptor antagonist AM630 group, and AM630 ＋ matrine 50 mg·kg^-1 group. The neurological scores and infarction volume were detected. HE stain was used to observe the pathological changes.TUNEL was used to measure the apoptosis cells, lmmunohistochemistry was used to observe the expression of cleaved caspase- 3 and Bcl- 2. RESULTS Compared with the model group, the neurological scores and infarction volume were decreased in matrine 20 mg·kg^-1 and matrine 50mg·kg^-1groups, as well as the pathological changes were relieved, the number of apoptotic cells and cleaved caspase- 3 expression were decreased, and Bcl-2 expression was increased （P 〈 0.05）. But these neuroprotective effects of matrine were abolished by pretreatment with AM630, there was significant difference between AM630 ＋ matrine 50 mg·kg^-1 group and matrine 50mg·kg^-1 group （P 〈 0.01） . CONCLUSION The activation of CB2 receptor might be involved in matrine induced neuroprotective effect on focal cerebral I/R injury.

关 键 词：苦参碱 受体 大麻酚 CB2 再灌注损伤 细胞凋亡 

分 类 号：R965[医药卫生—药理学]