摘要
目的:探讨蛇床子素改善急性心肌梗死大鼠心功能的效果及对心肌组织基质金属蛋白酶-2(MMP-2)和磷酸化细胞外信号调节激酶(p-ERK)的影响。方法:60只SD大鼠随机分成5组:正常对照组、模型组、依普利酮组(30 mg·kg^(-1))、蛇床子素低、高剂量组(20,40 mg·kg^(-1)),每组12只。除正常对照组外,其余各组建立急性心肌梗死模型,建模成功后,依普利酮组、蛇床子素低、高剂量组灌胃给予相应药物,正常对照组及模型组给予等体积生理盐水,1次/d,连续给药4周。给药结束后,苏木素-伊红(HE)染色观察心肌组织病理结构变化,测定大鼠左心室舒张末期内径(LVIDd)、短轴缩短分数(FS)、左心室收缩末期内径(LVIDs)、射血分数(EF)及心肌组织MMP-2、p-ERK mRNA和蛋白水平。结果:正常对照组心肌结构正常,肌纤维排列整齐;模型组心肌梗死区可见炎症细胞浸润,心肌纤维断裂,排列紊乱,可见明显梗死灶及瘢痕组织;依普利酮组及蛇床子素高剂量组心肌纤维排列较为整齐,梗死灶及瘢痕组织较少,炎症细胞浸润减少;蛇床子素低剂量组仍可见明显梗死灶及瘢痕组织,炎症细胞浸润也较为明显。与正常对照组比较,模型组大鼠LVIDd、LVIDs水平及MMP-2、p-ERK mRNA和蛋白水平升高,FS、EF水平降低(P<0.05);与模型组比较,依普利酮组、蛇床子素低、高剂量组LVIDd、LVIDs水平及MMP-2、p-ERK mRNA和蛋白水平降低,FS、EF水平升高(P <0.05);与依普利酮组比较,蛇床子素低剂量组各指标差异有统计学意义(P <0.05)。结论:蛇床子素对急性心肌梗死大鼠心功能具有明显改善作用,减轻心肌梗死大鼠心肌炎症氧化反应;其机制可能与蛇床子素能明显降低心肌组织MMP-2、p-ERK mRNA和蛋白水平有关。
Objective: To investigate the effects of osthol on cardiac function improvement and MMP-2 and p-ERK in myocardial tissue of rats with acute myocardial infarction.Methods: Totally 60 SD rats were randomly divided into 5 groups: normal control group,model group,epristone group(30 mg·kg^(-1)),osthol low and high dose groups(20,40 mg·kg^(-1)) with 12 in each group.Acute myocardial infarction model was established in the model group,epristone group,osthol low dose group and high dose group.After the successful modeling,rats in epristone group,osthol low dose group and high dose group were given corresponding drug by gavage,while rats in the normal control group and model group were given equal volume of physiological saline,once a day for 4 weeks.After the administration,hematoxylin eosin(HE) staining was used to observe the pathological changes of myocardial tissue,and left ventricular end-diastolic diameter(LVIDd),short axis shortening fraction(FS),left ventricular end-systolic diameter(LVIDs),ejection fraction(EF),and MMP-2,p-ERK mRNA and protein levels of myocardial tissue were measured.Results: In the normal control group,the myocardial structure was normal and the muscle fibers were arranged neatly;the myocardial infarction area in the model group showed inflammatory cell infiltration,myocardial fiber breakage,and the arrangement was disordered,and obvious infarction and scar tissue were seen;the arrangement of myocardial fibers in epristone group and osthole high dose group was relatively neat with fewer infarcts and scar tissues,and reduced inflammatory cell infiltration;obvious infarcts and scar tissues were still visible in osthole low dose group,and inflammatory cell infiltration was also obvious.Compared with those in the normal control group,the levels of LVIDd,LVIDs,MMP-2,p-ERK mRNA and protein in the model group were increased,and the levels of FS and EF were decreased(P <0.05).Compared with those in the model group,the levels of LVIDd,LVIDs,MMP-2,p-ERK mRNA and protein were decreased,and FS and EF le
作者
刘文华
徐恩国
杨建广
陶潞渊
Liu Wenhua;Xu Enguo;Yang Jianguang;Tao Luyuan(Department of Cardiology,Taizhou First People’s Hospital,Zhejiang Taizhou 318020,China)
出处
《中国药师》
CAS
2021年第3期416-420,共5页
China Pharmacist
基金
浙江省中医药科学研究基金项目(编号:2018ZA095)。