中国中药杂志

2017, v.42(20) 3974-3982

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降香新黄酮latifolin对大鼠急性心肌缺血影响及介导Nrf2信号通路机制研究
Effect of neoflavonoid latifolin isolated from Dalbergia odorifera on acute myocardial ischemia in rats and its mechanism of Nrf2 signaling pathway

李雪亮;陈兰英;官紫祎;骆瑶;崔亚茹;刘荣华;邵峰;王定清;
LI Xue-liang;CHEN Lan-ying;GUAN Zi-yi;LUO Yao;CUI Ya-ru;LIU Rong-hua;SHAO Feng;WANG Ding-qing;National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine,Jiangxi University of Traditional Chinese Medicine;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine;

摘要(Abstract):

研究降香新黄酮latifolin对垂体后叶素(Pit)及异丙肾上腺素(ISO)致大鼠急性心肌缺血保护作用及作用机制。Pit及ISO分别诱导大鼠急性心肌缺血,观察大鼠心电图变化。ISO诱导大鼠急性心肌缺血,ELISA法或比色法检测血清中心肌损伤标志物含量或活力、比色法检测心肌中SOD活力及MDA含量;HE染色进行组织病理学检查;心肌组织冰冻切片进行DCFH-DA荧光染色,检测心肌中ROS含量水平;Western blot法检测心肌中Nrf2,Keap1,HO-1及NQO1的蛋白表达水平。心电图结果显示,latifolin抑制Pit及ISO引起的ST段变化,抑制Pit引起心率减慢。机制研究结果显示,latifolin降低血清中c Tn I含量和AST及LDH活力;升高心肌中SOD活力,降低心肌中MDA含量;降低心肌组织炎细胞浸润、肌纤维断裂及坏死的程度;减弱心肌DCFH-DA荧光染色的荧光强度;抑制Keap1的蛋白表达,促进Nrf2核转移,促进HO-1及NQO1的蛋白表达。结果表明降香新黄酮latifolin对大鼠急性心肌缺血具有保护作用,主要机制可能与激活Nrf2信号通路从而发挥抗氧化作用有关。
The present study was designed to evaluate the cardioprotective effect of latifolin on pituitrin( Pit) or isoproterenol( ISO)-induced myocardial injury in rats,and further investigate its underlying mechanisms. Rats were administrated sublingually with pituitrin or subcutaneously with isoproterenol to induce acute myocardial ischemia in rats,and lead II electrocardiograph was recorded. In rats with isoproterenol,ELISA assay or colorimetric method was used to detect the content or activity of myocardial injury markers in serum,and the SOD activity and MDA content in myocardium were detected by colorimetric assay; histopathological examination was conducted by HE staining; the frozen section of myocardial tissues was used for DCFH-DA fluorescent staining to detect the content of ROS in myocardium; Western blot was used to detect the protein expression levels of Nrf2,Keap1,HO-1 and NQO1 in myocardium. Results showed that latifolin significantly inhibited ST-segment changes induced by pituitrin or isoproterenol,and increased heart rate. Further mechanism study showed that latifolin reduced cardiac troponin I( c Tn I) level,aspartate transaminase( AST) and lactate dehydrogenase( LDH) activities in serum,increased myocardial superoxide dismutase( SOD) activity and reduced myocardial malondialdehyde( MDA) level,and protected myocardium with less necrosis,infiltration of inflammatory cells and fracture of myocardial fibers. Furthermore,latifolin obviously reduced ROS level in myocardium,inhibited the expression of Kelch-like ECH-associated protein~(-1)( Keap1),increased the nuclear translocation of nuclear factor erythroid 2 related factor 2( Nrf2),and promoted the expression of Heme oxygenase-1( HO-1) and NAD( P) H quinone oxidoreductase-1( NQO1) in myocardial tissues. Our data suggest that latifolin has a potent protective effect against pituitrin or isoproterenol-induced myocardial injury,which may be related to inhibition of oxidative stress by activating Nrf2 signaling pathway.

关键词(KeyWords): latifolin;垂体后叶素;异丙肾上腺素;心肌缺血;Nrf2信号通路
latifolin;pituitrin;isoproterenol;myocardial injury;reactive oxygen species;Nrf2 signaling pathway

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基金项目(Foundation): 国家自然科学基金项目(81360629,81660676);; 江西省自然科学基金项目(20171BAB205096)

作者(Author): 李雪亮;陈兰英;官紫祎;骆瑶;崔亚茹;刘荣华;邵峰;王定清;
LI Xue-liang;CHEN Lan-ying;GUAN Zi-yi;LUO Yao;CUI Ya-ru;LIU Rong-hua;SHAO Feng;WANG Ding-qing;National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herbal Medicine,Jiangxi University of Traditional Chinese Medicine;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine;

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