氧化苦参碱对慢性心力衰竭大鼠心肌胞浆型磷脂酶A2、环氧合酶1、环氧合酶2、前列腺素I2合酶表达的影响  

Effect of Oxymatrine on Myocardial Cytosolic Phospholipase A2,Cyclooxygenase-1,Cyclooxygenase-2 and Prostacyclin Synthase Expression in Rat with Chronic Heart Failure

作　　者：徐烨华 马萍[2] 王洋 熊爱琴 戴贵东[4] 徐清斌[2] 

机构地区：[1]宁夏医科大学,宁夏银川市750004 [2]宁夏医科大学总医院心内科,宁夏银川市750004 [3]银川市口腔医院药剂科,宁夏银川市750004 [4]凯里学院化学与材料工程学院制药工程系,贵州省凯利市556011

出　　处：《中国动脉硬化杂志》2014年第10期973-980,共8页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(81060024)

摘　　要：目的探讨氧化苦参碱对异丙肾上腺素(ISO)诱导心力衰竭大鼠模型中心肌组织胞浆型磷脂酶A2(c PLA2)、环氧合酶1(COX-1)、环氧合酶2(COX-2)及前列腺素I2合酶(PGIS)的影响。方法采用Sprague-Dawley大鼠皮下注射ISO(5 mg/kg)7天建立慢性心力衰竭大鼠模型。实验分为5组:正常对照组、ISO组、氧化苦参碱100 mg/kg组、ISO+氧化苦参碱100 mg/kg组、ISO+氧化苦参碱50 mg/kg组。各组大鼠预先灌胃给药(不同剂量氧化苦参碱或等体积生理盐水)7天后,ISO组、ISO+氧化苦参碱(100 mg/kg、50 mg/kg)组大鼠灌胃给药同时皮下注射ISO(5 mg/kg),正常对照组、氧化苦参碱100 mg/kg组皮下注射等体积生理盐水7天,共14天。随后检测各组大鼠心功能血流动力学参数、血清脑钠肽含量,观察心肌病理学表现,用Western blot法对大鼠心肌c PLA2、COX-1、COX-2、PGIS进行半定量分析。结果氧化苦参碱(100 mg/kg、50 mg/kg)能改善心力衰竭心脏收缩和舒张功能,显著降低ISO诱导的心力衰竭大鼠升高的血清脑钠肽水平;氧化苦参碱可显著减轻心力衰竭大鼠的心肌纤维化,并且显著升高ISO诱导的心力衰竭大鼠心肌组织中COX-2、PGIS的表达(P<0.01),降低COX-1的表达(P<0.01);氧化苦参碱对ISO诱导的慢性心力衰竭大鼠心肌组织中c PLA2的表达无明显影响。结论氧化苦参碱可改善ISO诱导的心力衰竭大鼠的心脏功能及心肌纤维化,其机制可能与调节环氧合酶通路中COX-1、COX-2及PGIS的表达相关。Aim The present study was to investigate the protective effects of oxymatrine（ OMT） on regulation of the expression of cytosolic phospholipase A2（ c PLA2）,cyclooxygenase-1（ COX-1）,COX-2 and prostacyclin synthase（ PGIS） in isoproterenol-induced rat heart failure. Methods Heart failure was induced in Sprague-Dawley rats by 5mg / kg isoproterenol（ ISO） subcutaneous injection for 7 days. The rats,maintained on a normal diet,were randomly divided into five groups given control,oxymatrine（ 100 mg / kg） alone,ISO and ISO with oxymatrine（ 100 mg / kg or 50 mg /kg）. In groups of ISO and ISO with oxymatrine（ 100 mg / kg or 50 mg / kg）,saline or oxymatrine was administered orally for 7 days prior to the ISO administration. ISO（ 5 mg / kg） was administered subcutaneously for 7 days with saline or oxymatrine. In groups of control and oxymatrine（ 100 mg / kg） alone,saline was administered subcutaneously for 7 days.Serum brain natriuretic peptide（ BNP） level,haemodynamic parameters,histopathological variables and expression of protein levels were analysed. Results Oral administration of OMT significantly inhibited ISO-induced heart failure,as evaluated by serum BNP and haemodynamic parameters,and histological examinations. Coadministration of oxymatrine increased myocardial level of COX-2 and PGIS,and inhibited COX-1 expression in ISO-induced heart failure rat. Whereas the protein level for c PLA2 was markedly increased by ISO,OMT exerted no effects on ISO-induced elevated protein c PLA2 expression. Compared with control group,any indexes in sham rats treated with OMT（ 100 mg / kg） alone were unaltered（ all P 〉 0. 05）. Conclusion Our results suggest that the favourable effects of oxymatrine for management of heart failure are probably achieved by regulation of the COX-1,COX-2 and PGIS expression.

关 键 词：氧化苦参碱 异丙肾上腺素 心力衰竭 胞浆型磷脂酶A2 环氧合酶1 环氧合酶2 前列腺素I2合酶 大鼠 

分 类 号：R96[医药卫生—药理学]