芳香新塔花总黄酮对大鼠心肌缺血再灌注损伤的保护作用及机制  

Protective Effect and Mechanism of Ziziphora clinopodioides Flavonoids Against Myocardial Ischemia-reperfusion Injury in Rats

作　　者：申静 刘冲 陈文 SHEN Jing;LIU Chong;CHEN Wen(College of Pharmacy, Shihezi University, Key Laboratory of Xinjiang Phytomedicine Resources and Utilization, Ministry of Education, Shihezi 832000, China;Xinjiang Institute of Materia Medica , Urumqi 830000, China)

机构地区：[1]石河子大学药学院新疆植物药资源利用教育部重点实验室,石河子832000 [2]新疆维吾尔自治区药物研究所,乌鲁木齐830000

出　　处：《中国实验方剂学杂志》2018年第14期115-121,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81560714);自治区研究生科研创新项目(XJGRI2017040)

摘　　要：目的：探讨芳香新塔花总黄酮（Ziziphora clinopodioides flavonoids,ZCF）对大鼠心肌缺血再灌注损伤中氧自由基、一氧化氮（NO）和细胞凋亡的影响及其机制。方法：60只大鼠随机分为假手术组,缺血再灌注模型组,复方丹参滴丸组（130 mg·kg^-1）,ZCF低、中、高剂量组（75,150,300 mg·kg^-1）。通过结扎大鼠心脏冠状动脉左前降支30 min,再灌注3 h建立缺血再灌注损伤模型,测定大鼠血清中肌酸激酶同工酶（CK-MB）,乳酸脱氢酶（LDH）,超氧化物歧化酶（SOD）,谷胱甘肽过氧化物酶（GSH-Px）,丙二醛（MDA）,NO和一氧化氮合酶（NOS）等相关指标的变化。2,3,5-氯化三苯基四氮唑（TTC）染色法评价心肌梗死程度,苏木素-伊红（HE）染色法观察大鼠心肌组织病理学改变,原位末端转移酶标记法（TUNEL）检测细胞凋亡。实时荧光定量聚合酶链式反应法（Real-time PCR）检测B细胞淋巴瘤/白血病-2（Bcl-2）和Bcl-2相关X蛋白（Bax）mRNA的表达。结果：与假手术组比较,模型组大鼠血清中CK-MB,LDH,MDA的含量显著升高,SOD,GSH-Px,NO和NOS的活性显著降低,心肌梗死程度严重,出现明显的细胞凋亡,显著下调Bcl-2 mRNA表达,上调Bax mRNA表达（P〈0.01）。与模型组比较,ZCF给药组能明显降低大鼠血清中CK-MB,LDH,MDA的含量,提高SOD,GSH-Px,NO和NOS的活性,同时可降低心肌梗死面积,改善缺血心肌的病理变化,抑制细胞凋亡,显著上调Bcl-2 mRNA表达,下调Bax mRNA表达,提高Bcl-2/Bax水平（P〈0.05,P〈0.01）。结论：ZCF可减轻大鼠缺血心肌的损伤作用,其机制可能与减少氧自由基的产生,促进NO合成,上调Bcl-2mRNA的表达,下调Bax mRNA的表达,抑制细胞凋亡有关。Objective： To explore the effect and mechanism of Ziziphora clinopodioides flavonids（ ZCF）on oxygen free radicals,nitric oxide（ NO） and cell apoptosis of myocardial ischemia-reperfusion injury（ MIRI） in rats. Method： Totally 60 rats were randomly divided into sham group,MIRI model group,compound Danshen dripping pills group（ 130 mg·kg^-1）,low,medium and high-dose ZCF groups（ 75,150,300 mg·kg^-1）. The model of MIRI was established by ligating the left anterior descending coronary artery（ LAD） for 30 min,which was followed by a 3 h reperfusion. The levels of creatine kinase isozyme（ CK-MB）,lactate dehydrogenase（ LDH）,superoxide dismutase（ SOD）,glutathione peroxidase（ GSH-Px）,malondialdehyde（ MDA）,nitric oxide（ NO） and nitric oxide synthase（ NOS） in serum were measured. The degree of myocardial infarction was evaluated by triphenyltetrazolium chlorid（ TTC） staining,the pathological changes of myocardium in rats were observed by hematoxylin and eosin（ HE） staining, and the cell apoptosis was detected by terminaldeoxynucleoitidyl transferase mediated nick end labeling（ TUNEL）. Quantitative Real-time PCR was utilized to measure Bcl-2 and Bax mRNA expressions. Result： Compared with the shame group,the content of CK-MB,LDH,MDA showed significant increases,while the activities of SOD,GSH-Px,NO and NOS showed significant decreases in the model group. It also showed severe myocardial infarction and obvious cell apoptosis. The expression of Bcl-2 mRNA was significantly down-regulated,and the expression of Bax mRNA was significantly upregulated（ P〈0. 01）. Compared with the model group,ZCF significantly decreased the content of CK-MB,LDH,MDA,and increased the activities of SOD,GSH-Px,NO and NOS. At the same time,the area of myocardial infarction was reduced,the pathological changes of ischemic myocardium were alleviated,and the cell apoptosis of myocardium was inhibited. The expression of Bcl-2 was significantly up-regulated, whereas the Bax mRNA exp

关 键 词：芳香新塔花总黄酮 心肌缺血再灌注 氧自由基 一氧化氮 细胞凋亡 

分 类 号：R22[医药卫生—中医基础理论] R24[医药卫生—中医学]