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目的:探讨黄芪甲苷(astragaloside IV)通过TLR4/p38MAPK信号通路对脂多糖(LPS)诱导的C57BL/6J小鼠急性心肌损伤的作用,并阐明其作用机制。方法:小鼠30只随机分为5组,分为空白对照组、脂多糖组、黄芪甲苷40mg/kg组、黄芪甲苷80mg/kg组、3-去氮腺苷10mg/kg(阳性对照)组。黄芪甲苷给药组给予黄芪甲苷14 d、3-去氮腺苷组给予3-去氮腺苷14 d后,腹腔注射脂多糖建立急性内毒素心肌损伤模型。采用射血分数(EF)、缩短分数(FS)、左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)等指标观察小鼠心脏功能;采用免疫组化检测心肌组织中ED1炎性细胞浸润情况;Western Blot检测TLR4、p38MAPK、pp38MAPK的表达情况;应用酶联免疫吸附测定法(ELISA)检测血清中TNF-α、IL-1β、IL6的含量;采用RT-PCR检测心肌组织中BNP mRNA的表达情况。结果:与空白对照组相比,脂多糖组的射血分数(EF)、缩短分数(FS)、左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)明显降低,而血清中TNF-α、IL-1β和IL6含量增加,组织中ED1、TLR4、p38MAPK、p-p38MAPK的表达明显增加。与脂多糖组相比,黄芪甲苷(40、80mg/kg)组均能明显提高EF、FS、LVIDd、LVIDs,以及明显降低TNF-α、IL-1β、IL6的含量及ED1、TLR4、p38MAPK、p-p38MAPK的表达。结论:黄芪甲苷对脂多糖引起的心肌炎症具有明显的抑制作用,可能是通过TLR4/p38MAPK信号通路起作用,并有效改善由脂多糖导致的心肌损伤。
AIM: To investigate the effect of astragaloside IV on acute myocardial injury induced by lipopolysaccharide (LPS) in C57BL / 6J mice through TLR4 / p38MAPK signaling pathway and to elucidate its mechanism. Methods: Thirty mice were randomly divided into five groups and divided into blank control group, lipopolysaccharide group, Astragaloside 40mg / kg group, Astragaloside 80mg / kg group and 3-deazadenosine 10mg / kg (positive control )group. Astragaloside administration group was given astragaloside 14 d, 3-deaza adenosine group was given 3-deaza adenosine 14 d, intraperitoneal injection of lipopolysaccharide to establish acute endotoxin myocardial injury model. The cardiac function of mice was observed by the indexes of ejection fraction (EF), fractional shortening (FS), left ventricular end diastolic dimension (LVIDd) and left ventricular end-diastolic dimension (LVIDs). The expression of ED1 in myocardium The expression of TLR4, p38MAPK and pp38MAPK were detected by Western Blot. The levels of TNF-α, IL-1β and IL6 in serum were detected by enzyme linked immunosorbent assay (ELISA). The levels of BNP mRNA expression. Results: Compared with the blank control group, the ejection fraction (EF), shortening fraction (FS), left ventricular end diastolic dimension (LVIDd), and left ventricular end-systolic dimension (LVIDs) α, IL-1βand IL6 increased, the expression of ED1, TLR4, p38MAPK and p-p38MAPK in the tissues increased obviously. Compared with lipopolysaccharide group, the levels of EF, FS, LVIDd, LVIDs and the levels of TNF-α, IL-1β, IL6 and ED1, TLR4, p38MAPK , P-p38MAPK expression. CONCLUSION: Astragaloside has a significant inhibitory effect on lipopolysaccharide-induced myocardial inflammation, which may be through the TLR4 / p38MAPK signal pathway and effectively improve myocardial injury caused by lipopolysaccharide.