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茯苓四逆汤抑制TLR4/NF-κB通路改善慢性心衰大鼠心功能 被引量:1

Fuling Sini Decoction Inhibits TLR4/NF-κB Pathway and Improves Cardiac Function in Rats with Chronic Heart Failure
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摘要 目的:探讨茯苓四逆汤对慢性心衰大鼠心功能的影响以及可能的分子机制。方法:采用腹腔注射阿霉素法复制慢性心衰大鼠模型,造模成功大鼠随机分为模型组、茯苓四逆汤低、中、高剂量组(6g/kg、12g/kg、18g/kg)、卡托普利组(2.25mg/kg)。腹腔注射生理盐水的12只大鼠作为对照组。超声心电图检测心功能指标;ELISA检测血清肿瘤坏死因子-α(TNF-α)、白介素(IL)-1β、IL-6水平;HE染色观察心肌组织病理学改变;TUNEL染色观察心肌细胞凋亡率;Western blot检测大鼠心肌组织中Toll样受体4(TLR4)、核因子-κB(NF-κB)、p-NF-κB、核因子κB抑制蛋白α(IκBα)、p-IκBα蛋白表达。结果:与对照组比较,模型组大鼠左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)升高(P<0.05),左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、血清TNF-α、IL-1β、IL-6水平升高,心肌组织病理损伤程度加重,心肌细胞凋亡率以及心肌组织中TLR4、p-NF-κB/NF-κB、p-IκBα/IκBα蛋白表达水平升高(P<0.05)。与模型组比较,茯苓四逆汤低、中、高剂量组和卡托普利组大鼠LVEF、LVFS升高(P<0.05),LVESD、LVEDD、血清TNF-α、IL-1β、IL-6水平降低,心肌组织病理损伤程度减轻,心肌细胞凋亡率以及心肌组织中TLR4、p-NF-κB/NF-κB、p-IκBα/IκBα蛋白表达水平降低(P<0.05)。结论:茯苓四逆汤能够抑制TLR4/NF-κB通路激活,减轻慢性心衰大鼠心肌损伤,改善心功能。 Objective:To investigate the influences of Fuling Sini Decoction on cardiac function in rats with chronic heart failure and the possible molecular mechanism.Methods:The rat model of chronic heart failure was established using intraperitoneal injection of doxorubicin.Rats that were successfully modeled were randomly divided into the model group,low,medium,and high-dose Fuling Sini Decoction groups(6 g/kg,12 g/kg,18 g/kg),and a captopril group(2.25mg/kg),with 12 rats in each group.An additional 12 rats were intraperitoneally injected with normal saline as the control group.Cardiac function indicators were assessed using echocardiography;serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 were measured using ELISA;myocardial tissue histopathological changes were observed using HE staining;cardiomyocyte apoptosis rates were determined through TUNEL staining;Western blot was employed to measure the expression levels of Toll-like receptor 4(TLR4),nuclear factor-κB(NF-κB),p-NF-κB,nuclear factorκB inhibitory proteinα(IκBα),and p-IκBαproteins in myocardial tissue.Results:Compared to the control group,rats in the model group exhibited increased left ventricular ejection fraction(LVEF)and left ventricular short-axis shortening rate(LVFS)(P<0.05),as well as increased left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),serum levels of TNF-α,IL-1β,and IL-6.The degree of myocardial tissue pathological injury worsened,and there was an increase in cardiomyocyte apoptosis rates and the expression levels of TLR4,p-NF-κB/NF-κB,and p-IκBα/IκBαproteins in myocardial tissue(P<0.05).Compared to the model group,rats in the low,medium,and high-dose Fuling Sini Decoction groups and the captopril group exhibited increased LVEF and LVFS(P<0.05),decreased LVESD,LVEDD,serum TNF-α,IL-1β,and IL-6 levels,and reduced pathological damage in myocardial tissue.There was also a decrease in cardiomyocyte apoptosis rates and the expression levels of TLR4,p-NF-κB/NF-κ
作者 张梦 李晶晶 樊光辉 ZHANG Meng(Hubei University of Chinese Medicine/Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei Wuhan 430000,China)
出处 《河北医学》 CAS 2023年第11期1772-1777,共6页 Hebei Medicine
基金 武汉市中医药科研项目,(编号:WZ22C55)。
关键词 茯苓四逆汤 慢性心力衰竭 TLR4/NF-κB通路 Fuling sini decoction Chronic heart failure TLR4/NF-κB pathway
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