摘要
目的:研究参麦注射液对慢性心力衰竭(CHF)模型大鼠心脏功能改善的作用机制。方法:将40只大鼠按照随机数字表法分为假手术组(0.9%氯化钠注射液,肌内注射)、模型组(0.9%氯化钠注射液,肌内注射)、阳性对照组(缬沙坦10 mg/kg,灌胃给药)和SMI组(参麦注射液0.38 mL/kg,肌内注射),每组10只。除假手术组外,其余各组大鼠均采用左冠状动脉前降支结扎法制备CHF模型。造模成功后,每组大鼠1日给药1次,连续28 d。采用超声心动仪观测大鼠左心室变化并结合血流动力学改变评估心功能状况,应用酶联免疫吸附试验测定N末端B型利钠肽原(NT-proBNP)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)、结缔组织生长因子(CTGF)水平,利用苏木精-伊红染色及MASSON染色观察心肌形态学变化。通过实时定量逆转录聚合酶链式反应检测TGF-β1、Smad蛋白(Smad)2、Smad3及Smad7表达水平。结果:与假手术组相比,模型组大鼠左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、收缩末期左心室后壁厚度(LVPWs)、流出道血流峰值、左心室内压(LVP)、左心室收缩压(LVSP)、左心室压力最大上升速率和最大下降速率(+dp/dt_(max),-dp/dt_(min))均明显降低,收缩末期左心室容积(LV Vols)、内径(LVIDs)和左心室舒张末压(LVEDP)明显升高;血清NT-proBNP、TGF-β1、MMP-9和CTGF水平显著升高;心肌组织中TGF-β1、Smad2、Smad3的mRNA表达程度升高,Smad7 mRNA表达程度降低,上述差异均有统计学意义(P<0.01)。形态学结果显示,CHF大鼠存活心肌细胞少,结构凌乱,纤维化程度严重。与模型组相比,SMI组可显著提升CHF大鼠心脏LVEF、LVFS和LVPWs水平,减少LV vols、LVIDs,改善血流动力学情况,降低NT-proBNP、TGF-β1、MMP-9和CTGF水平,显著下调心肌TGF-β1、Smad2、Smad3 mRNA表达并上调Smad7 mRNA表达水平,差异均有统计学意义(P<0.01)。参麦注射液可抑制心肌细胞坏死,减轻心肌纤维化�
OBJECTIVE:To probe into the mechanism of Shenmai injection(SMI)on improving ventricular remodeling in rats with chronic heart failure(CHF).METHODS:According to random number table method,40 rats were divided into sham surgery group(0.9%sodium chloride injection,intramuscular injection),model group(0.9% sodium chloride injection,intramuscular injection),positive control group(valsartan 10 mg/kg,intramuscular injection)and SMI group(Shenmai injection 0.38 mL/kg,intramuscular injection),with 10 rats in each group.Except for sham surgery group,another groups were established CHF model by ligation of left anterior descending coronary artery.After establishment of the model,the related drugs were administered once a day for 28 d.Echocardiography was applied to observe the changes of left ventricular and evaluate situation of cardiac function based on hemodynamics.Enzyme-linked immunosorbent assay(ELISA)were performed to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP),transforming growth factor-β1(TGF-β1),matrix metalloproteinases 9(MMP-9)and connective tissue growth factor(CTGF).Morphological changes of myocardium were observed by hematoxylin-eosin(HE)staining and MASSON staining.Expression levels of TGF-β1,Smad2,Smad3 and Smad7 were detected through quantification reverse transcription polymerase chain reaction.RESULTS:Compared with the sham group,the left ventricular ejection fraction(LVEF),left ventricular short-axis shortening rate(LVFS),left ventricular posterior wall thickness(LVPWs),aortic flow peak velocity(AV Peak Velocity),left ventricular pressure(LVP),left ventricular systolic pressure(LVSP),+dp/dt_(max) and-dp/dt_(min) in the model group decreased significantly;and left ventricular volume(LV vols),left ventricular end-systolic diameter(LVIDs),left ventricular end diastolic pressure(LVEDP)increased significantly;the serum levels of NT-proBNP,TGF-β1,MMP-9 and CTGF decreased significantly;the mRNA expression of TGF-β1,Smad2,and Smad3 increased significantly,the mRNA expression
作者
施洋
张晟肇
陈振东
曹永宏
王辉
杨英来
王洋洋
SHI Yang;ZHANG Shengzhao;CHEN Zhendong;CAO Yonghong;WANG Hui;YANG Yinglai;WANG Yangyang(Dept.of Pharmacy,Karamay Municipal Hospital of Integrated Traditional Chinese and Western Medicine(Karamay Municipal Peoples’Hospital),Xinjiang Karamay 834000,China;Research Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Dept.of Pharmacy,Karamay Hospital,People’s Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Karamay 834000,China;Dept.of Laboratory,Karamay Municipal Hospital of Integrated Traditional Chinese and Western Medicine(Karamay Municipal Peoples’Hospital),Xinjiang Karamay 834000,China;College of Pharmacy,Xinjiang Second Medical College,Xinjiang Karamay 834000,China)
出处
《中国医院用药评价与分析》
2024年第9期1025-1029,1034,共6页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
国家自然科学基金资助项目(No.81774050)
新疆维吾尔自治区青年科学基金项目(No.2022D01B194)
克拉玛依市首届科技创新人才培养项目(No.克科发〔2023〕1号)
克拉玛依市中西医结合医院(市人民医院)院级科研项目(No.Kzxy2023003)。