摘要
目的：研究生脉散对扩张型心肌病（dilated cardiomyopathy，DCM）大鼠的干预作用，探讨生脉散对Toll样受体4（Tolllikereceptor-4，TLR-4）／核转录因子-κB（nuclear factor kappaB，NF-κB）信号通路及炎症因子的影响。方法：用腹腔注射阿霉素法建立DCM大鼠模型，将大鼠随机分为空白组、阿霉素组、生脉散组、培哚普利组，分别采用生脉散和培哚普利对DCM大鼠进行干预。治疗后对大鼠行心脏超声检查；用酶联免疫吸附测定法（ELISA）检测血清B型钠尿肽（BNP），肿瘤坏死因子-α（TNF-α）及白细胞介素一6（IL-6）水平；用实时荧光定量PCR法（Real-timePCR）法检测心肌组织TLR-4，NF-κBmRNA表达水平；用蛋白质印迹法（Westernblot）检测心肌组织TLR-4，NF-κB蛋白表达水平；取大鼠左室心肌组织用苏木素一伊红（HE）染色和透射电子显微镜的方法观察大鼠心肌组织形态。结果：与空白组比较，阿霉素组左室舒张末期内径（LVIDd），左室收缩末期内径（LVIDs）增大（P〈0．01），左心室射血分数（LVEF），短轴缩短率（FS）下降（P〈0．01）；血清BNP，TNF-α，IL-6水平升高（P〈0．01）；心肌组织TLR-4，NF-KBmRNA及蛋白表达水平升高（P〈0．01）；心肌组织病理损伤增加。与阿霉素组比较，生脉散组LVIDs，LVIDd减小（P〈0．01），LVEF，FS增加（P〈0．01）；血清BNP，TNF-α，IL-6水平下降（P〈0．01）；心肌组织TLR-4，NF-KBmRNA及蛋白表达水平下降（P〈0．01），心肌组织病理损伤有所改善。结论：生脉散可有效改善DCM大鼠心功能，抑制心肌损害。生脉散治疗DCM大鼠的作用机制，可能与调节TLR-4和NF-κBmRNA及蛋白水平从而抑制TLR-4／NF-KB信号通路下游炎症因子有关。
Objective： To evaluate the effect of Shengmaisan on rats with dilated cardiomyopathy （DCM）, Toll-like receptor-4 （TLR-4） /nuclear factor kappa-light-chain-enhancer of activated B cells （NF-KB） signaling pathway as well as inflammatory factors. Method： The establishment of dilated cardiomyopathy rats model was induced through intraperitoneal injection with doxorubicin （ 1 mg · kg-1, twice a week） for 6 weeks, and then observed for 2 weeks, which lasted for eight weeks in total. The rats were randomly divided into four groups ： blank group, doxorubicin group, Shengmaisan group and perindopril group. The drug groups were given Shengmaisan and perindopril, while blank group and model group were given equal volume of normal saline, left ventricular internal diameter at end-diastole （LVIDd）, left ventricular internal dimenter at end-systole （LVIDs）, left ventricular ejection fraction （LVEF） and fractional shortening （FS） were measured by echocardiography. Then the levels of serum brain natriuretic peptide （BNP） and inflammatory factors, including tumor necrosis factor-a （TNF-a） and interleukin-6 （IL-6） were tested by enzyme-linked immunosorbent assay （ELISA）. TLR-4, NF-KB mRNAs and proteins expressions in rat cardiac muscle were respectively determined. Histopathological characteristics of left ventricular cardiac muscle were observed by hematoxylin-eosin （HE） staining and transmission electron microscopy. Result： Compared with blank group, LVIDd and LVISd in the doxorubicin group were increased significantly （P 〈 0.01）; LVEF and FS were decreased significantly. Rats serum BNP, TNF-a and IL-6 levels increased significantly （P 〈 0.01 ） ; TLR4, NF-KB mRNA and protein expressions were increased significantly （P 〈 0.01 ）. And the pathological damage of myocardium was increased. Compared with doxorubicin group, LVIDd and LVISd in the Shengmaisan group were decreased significantly （P 〈 0.01 ）; LVEF and FS were increased significantly, Rat se
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2018年第2期128-134,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
无锡市医院管理中心科研项目(YGZXM14047)
关键词
扩张型心肌病
生脉散
培哚普利
TOLL样受体-4
核转录因子-κB
炎症因子
dilated cardiomyopathy
Shengmaisan
perindopril
Toll-like receptor-4 （TLR-4）
nuclearfactor kappa-light-chain-enhancer of activated B cells （NF-KB）
inflammatory factor
