苦参素对大鼠脑缺血后脑线粒体损伤保护作用的研究Protective Effects of Oxymatrine on Brain Mitochondrial Damage after Cerebral Ischemia
余婷,韩亚非
摘要(Abstract):
目的研究苦参素对大鼠脑缺血后脑线粒体的保护作用。方法采用线栓法制备局灶性脑缺血再灌注大鼠模型,设假手术组、模型组和苦参素低(25mg/kg)、中(50mg/kg)、高(100mg/kg)剂量组,各20只,分别于术前10min腹腔注射给药。24h后,测定缺血侧脑线粒体肿胀程度、膜流动性、呼吸功能,电子显微镜观察线粒体超微结构变化,测定线粒体内超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,MDA含量,Na~+-K~+-ATPase、Ca~(2+)-Mg~(2+)-ATPase活性,游离Ca~(2+)浓度。结果与模型组比较,经苦参素中、高剂量预处理能够明显改善大鼠脑缺血后线粒体肿胀,提高膜流动性,改善线粒体呼吸功能,抑制线粒体超微结构损伤,显著提高SOD、GSH-Px活性并降低MDA含量(P<0.05或P<0.01),显著提高Na~+-K~+-ATPase、Ca~(2+)-Mg~(2+)-ATPase活性(P<0.05或P<0.01),降低游离Ca~(2+)浓度(P<0.05)。结论苦参素对脑缺血后脑线粒体损伤具有一定的保护作用,其机制可能与降低Ca~(2+)浓度、抑制氧化应激损伤以及改善ATPase活性有关。
关键词(KeyWords): 苦参素;脑缺血;线粒体;氧化应激;ATPase;Ca2+
基金项目(Foundation): 河北省邯郸市科学技术研究与发展计划项目(1623208070ZC)
作者(Author): 余婷,韩亚非
参考文献(References):
- [1]颜娟,郑茂东,崔玉环,等.牡荆苷对脑缺血再灌注损伤小鼠脑组织能量代谢的影响[J].山东医药,2017,57(5):26-29.
- [2]秦胜利.红花注射液对大鼠脑缺血再灌注损伤后能量代谢的影响[J].临床医学,2016,36(7):114-116.
- [3]孙明,赵育梅,徐超.牛磺酸降低局灶性脑缺血引起的能量代谢紊乱和氧化损伤[J].中风与神经疾病杂志,2008,25(5):577-579.
- [4]Zheng L,Ding J,Wang J,et al.Effects and mechanism of action of inducible nitric oxide synthase on apoptosis in a rat model of cerebral ischemia-reperfusion injury[J].Anat Rec(Hoboken),2016,299(2):246-255.
- [5]黄秀梅,李波,等.氧化苦参碱对TNFA、IL-6和IL-8的影响[J].中成药,2003,25(11):903-906.
- [6]孔秀岩,苏志刚.氧化苦参碱对细胞凋亡影响的研究现状[J].河北医药,2007,29(12):1371-1373.
- [7]王雪芬,王磊,陈树杰.苦参素对大鼠心肌缺血再灌注损伤的保护作用及其机制研究[J].中国中医急症,2016,25(6):988-992.
- [8]缪培,张通,米海霞,等.基于线栓法大鼠大脑中动脉闭塞的局灶性脑缺血模型的比较研究[J].中国康复理论与实践,2016,22(10):1190-1195.
- [9]Zhang HX,Du GH,Zhang JT.Ischemic pre-conditioning preserves brain mitochondrial functions during the middle cerebral artery occlusion in rat[J].Neurol Res,2003,25:471-476.
- [10]Xiong J,Feng YP.The protective effect of butylphthalide against mitochondrial injury during cerebral ischemia[J].Acta Pharm Sin,2000,35(6):408-412.
- [11]Kobayashi T,Kuroda S,Tada M,et al.Calcium-induced mitochondrial swelling and cytochrome c release in the brain:its biochemical characteristics and implication in ischemic neuronal injury[J].Brain Res,2003,960(1-2):62-70.
- [12]Xi T,Rao MR.Effects of mnifedipine on left ventricular diastolic function and Ca2+content of myocardial and cerebral mitochondria and artery tissues in left ventircular hypertrophied rats[J].Acta Pharm Sin,1995,30(1):6-11.
- [13]Chan PH.Mitochontria and neuronal death/survival signaling pathways in cerebral ischemia[J].Neurochem Res,2004,29:1943-1949.
- [14]高鹏.苦参素抗大鼠肝脏缺血再灌注损伤作用的研究[J].当代医学,201,16(14):15-17.
- [15]贾昌盛,孙建军,李美德,等.苦参素降低大鼠肾脏缺血-再灌注损伤[J].基础医学与临床,2012,32(8):943-947.
- [16]程钢,秦媛媛,程迪,等.氧化苦参碱对大鼠局灶性脑缺血损伤的保护作用及其抑制凋亡的作用机制[J].中国药理学通报,2013,29(3):387-392.
- [17]陈利平,王发渭,韩志涛,等.苦参碱对脑缺血再灌注损伤炎性因子的影响[J].中国中医急症,2010,19(12):2098-2099.
- [18]Korge P,Honda HM,Weiss JN.Regulation of the mitochondrial permeability transition by matrix Ca2+and voltage during anoxia-reoxygenation[J].Am J Physiol,2001,280:517-526.
- [19]Lartigue A,Burlat B,Coutard B,et al.The Megavirus chilensis Cu,Zn-superoxide dismutase:the first viral structure of a typical cellular copper chaperone-independent hyperstable dimeric enzyme[J].J Virol,2015,89(1):824-832.
- [20]Kwiecien S,Magierowska K,Magierowski M,et al.Role of sensory afferent nerves,lipid peroxidation and antioxidative enzymes in the carbon monoxide-induced gastroprotection against stress ulcerogenesis[J].J Physiol Pharmacol,2016,67(5):717-729.
- [21]Maciel EN,Kowaltowski AJ,Schwalm JM,et al.Mitochondrial permeability transition in neuronal damage promoted by Ca2+and respiratory chain complexⅡinhibition[J].J Neurochem,2004,90(5):1025-1031.
- [22]常明则,乔琳,吴海琴,等.葛根素预处理对大鼠局灶性脑缺血-再灌注线粒体功能的影响[J].脑与神经疾病杂志,2014,22(4):278-280.