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作 者:王勇 刘学武 代志 石镇港 曾贵荣 WANG Yong;LIU Xue-wu;DAI Zhi;SHI Zhen-gang;ZENG Gui-rong(China Resources Sanjiu Medical&Pharmaceutical Co.,Ltd.,Guangdong 518029,China;Hunan Center of Drug Safety Evaluation and Research of Drugs&Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs,Changsha 410331,China;Key Laboratory of Traditional Chinese Medicine Power and Innovative Drugs of Hunan,Changsha 410208,China)
机构地区:[1]华润三九医药股份有限公司,广东518029 [2]湖南省药物安全评价研究中心&新药药效与安全性评价湖南省重点实验室,长沙410331 [3]湖南省中药粉体与创新药物省部共建国家重点实验室培育基地,长沙410208
出 处:《中国新药杂志》2019年第24期3010-3015,共6页Chinese Journal of New Drugs
基 金:湖南省科技厅重点研发计划资助项目(2018SK2115)。
摘 要:目的:研究参附注射液对大鼠离体心肌缺血再灌注心肌组织自噬的调控作用。方法:采用Langendorff离体灌流系统建立大鼠离体心脏缺血再灌注模型,给予0. 5%,1%和2%参附注射液,检测不同时间心功能指标、灌流液心肌酸激酶(creatine kinase,CK)、心肌酸激酶同工酶[creatine kinase,MB form (CKMB)]、乳酸脱氢酶(lactate dehydrogenase,LDH)含量以及心肌组织中自噬标志蛋白Beclin-1,LC3的表达。结果:0. 5%参附注射液能明显降低灌流液LDH含量,1%,2%参附注射液能明显降低灌流液CK,CK-MB,LDH含量,增加心肌缺血再灌注模型心率、左心室发展压(left ventricularend-diastolic pressure,LVDP)、左心室内压力下降最大速率(-dp/dtmax)、左心室内压力上升最大速率(+dp/dtmax),降低心肌组织Beclin-1,LC3Ⅱ/LC3Ⅰ蛋白表达。结论:参附注射液可通过抑制心肌自噬过度激活,发挥心肌保护作用。Objective: To study the regulation effect of Shenfu injection on myocardial ischemia reperfusion autophagy in rats. Methods: Langendorff perfusion system in vitro was used to establish in vitro cardiac ischemia reperfusion model in rats. After giving 0. 5%,1%,and 2% injections,cardiac function indexes,levels of creatine kinase (CK),creatine kinase,MB form (CK-MB),and lactate dehydrogenase (LDH) and the expressions of autophagy marker protein Beclin-1 and LC3 in myocardial tissue at different time were detected. Results: 0. 5% Shenfu injection could significantly reduce the LDH content in the perfusion fluid. 1% and 2% Shenfu injections significantly reduced the CK,CK-MB,LDH contents in the perfusion fluid,increased heart rate,left ventricularenddiastolic pressure (LVDP),maximum rate of left heart indoor pressure decrease(-dp/dtmax),and maximum rate of left heart largest indoor pressure rise (+ dp/dtmax),and reduced the expressions of Beclin-1 and LC3Ⅱ/LC3 Ⅰ protein in myocardial tissue. Conclusion: Shenfu injection can protect myocardium by inhibiting excessive activation of autophagy in cardiomyocytes.
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