目的 探讨黄芪甲苷（Astragaloside IV，ASIV）对脂多糖（lipopolysaccharide，LPS）诱导的小鼠脓毒症心肌病及过氧化物酶体增殖物激活受体α（PPARα）的影响。 方法 50只健康雄性C57BL/6J小鼠随机分为5组，每组10只，分为空白对照组、脂多糖模型组、ASIV（20、40、80 mg·kg-1·d-1）组。ASIV组灌胃ASIV 7 d，然后同模型组给予脂多糖10 mg/kg一次性腹腔注射建立急性内毒素损伤模型。8 h后超声观察小鼠心功能指标：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）；HE染色观察小鼠心脏组织形态学变化；酶联免疫吸附测定肿瘤坏死因子（TNF- α）、白介素-1β（IL-1β）、白介素-6（IL-6）、游离脂肪酸（FFA）的表达水平；高效液相色谱法检测三磷酸腺苷（ATP）、二磷酸腺苷（ADP）、单磷酸腺苷（AMP）的含量；Western blot法检测心肌组织中PPARα、ATP5D的蛋白表达水平。 结果 与模型组相比，ASIV组的心功能指标EF、FS、LVIDd、LVIDs提高，改善了心肌组织的炎性细胞浸润、心肌纤维变形，TNF-α、IL-1β、IL-6、FFA的表达减少，ATP/AMP、ADP/AMP比值增加，PPARα、ATP5D的蛋白表达增多。 结论 ASIV可能是通过PPAR改善脂多糖诱导的心肌损伤能量代谢水平，对脓毒症心肌病起到保护作用。
Abstract
Objective To investigate the effects of Astragaloside IV (ASIV) on myocardial myocardiopathy and peroxisomal proliferate activation receptor α (PPARα) in mice induced by lipopolysaccharide (LPS). Methods 50 healthy male C57BL/6J mice were randomly divided into 5 groups, each group of 10 mice, which were divided into a blank control group, a lipopolysaccharide model group and three astragaloside IV (20, 40, 80 mg/kg/d) groups. Astragaloside IV was administered to the ASIV groups for 7 days, and then the model group was given LPS (10 mg/kg) to establish an acute endotoxin damage model. After 8 h, ultrasound was used to observe the mouse heart function index: ejection fraction (EF), shortening fraction (FS), left ventricular diastolic inner diameter (LVIDd), and left ventricular end-systolic diameter (LVIDs); HE staining was used to observe the morphological changes of the heart tissue of mice; Enzyme linked immunosorbent assay (ELISA) was used to detect tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and free fatty acid (FFA); High performance liquid chromatography (HPLC) was used to detect the content of adenosine triphosphate (ATP), adenosine diphosphate(ADP) and adenosine monophosphate (AMP); Western Blot was used to detect the protein expression levels of PPARα and ATP5D in myocardial tissues. Results Compared with the model group, the increasing of the cardiac function index EF, FS, LVIDd and LVIDs of the ASIV groups improved the infiltration of inflammatory cells and the deformation of myocardial fibers, decreased the content of TNF-α, IL-1β, IL-6, FFA, and increased the ratio of ATP/AMP and ADP/AMP ; increased the protein expressions of PPARα and ATP5D. Conclusions Astragaloside IV may be used to improve the energy metabolism of myocardial injury induced by lipopolysaccharide by PPARα, which can protect the cardiomyopathy of sepsis.
关键词
ASIV /
脂多糖 /
脓毒症心肌病 /
过氧化物酶体增殖物激活受体α /
能量代谢
Key words
/
Astragaloside IV /
Lipopolysaccharide /
Sepsis cardiomyopathy /
PPARα /
Energy metabolism
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参考文献
[1] Kimmoun A, Ducrocq N, Levy B, et al. Mechanisms of vascular hyporesponsiveness in septic shock[J]. Curr Vasc Pharmacol, 2013, 11(2): 139-149.
[2] Merx MW, Weber C. Sepsis and the heart[J]. Circulation, 2007, 116(7): 793-802.
[3] Gilde AJ, van der Lee KA, Willemsen PH, et al. Peroxisome proliferator-activatedreceptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism[J]. Circ Res, 2003, 92(5): 518-524.
[4] Suzuki M, Nakamura F, Taguchi E, et al. 4',6-Dimethoxyisoflavone-7-O-β-D-glucopyranoside (wistin) is a peroxisome proliferator-activatedreceptor α (PPARα) agonist in mouse hepatocytes[J]. Mol Cell Biochem, 2018, 446(1-2): 35-41.
[5] Kaimoto S, Hoshino A, Arlyoshi M, et al. Activation of PPAR-alpha in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure[J]. Am J Physiol Heart Circ Physiol, 2017, 312(2): H305-H313.
[6] Kodde IF, van der Stok J, Smolenski RT, et al. Metabolic and genetic regulationof cardiac energy substrate preference[J]. Comp Biochem Physiol A Mol Integr Physiol, 2007, 146(1): 26-39.
[7] Mei M, Tang F, Lu M, et al. Astragaloside IV attenuates apoptosis of hypertrophic cardiomyocyte through inhibiting oxidative stress and calpain-1 activation[J]. Environ Toxicol Pharmacol, 2015, 40(3): 764-773.
[8] Li L, Hou X, Xu R, et al. Research review on the pharmacological effects of astragaloside IV[J]. Fundam Clin Pharmacol, 2017, 31(1): 17-36.
[9] Zhang S, Tang F, Yang Y, et al. Astragaloside IV protects against isoproterenol-induced cardiac hypertrophy by regulating NF-κB/PGC-1α signaling mediated energy biosynthesis[J]. PLoS One, 2015, 10(3): e0118759.
[10]Uchihashi M, Hoshino A, Okawa Y, et al. Cardiac-specific Bdh1 overexpression ameliorates oxidative stress and cardiac remodeling in pressure overload induced heart failure[J]. Circ Heart Fail, 2017, 10(12): e004417.
[11]Rowe GC, Jiang A, Arany Z, et al. PGC-1 coactivators in cardiac development and disease[J]. Circ Res, 2010, 107(7): 825-838.
[12]Finck BN. The PPAR regulatory system in cardiac physiology and disease[J]. Cardiovasc Res, 2007, 73(2): 269-277.
[13]Azevedo PS, Minicucci MF, Santos PP, et al. Energy metabolism in cardiac remodeling and heart failure[J]. Cardiol Rev, 2013, 21(3): 135-140.
[14]Pol CJ, Lieu M, Drosatos K, et al. PPARs: protectors or opponents of myocardial function[J]. PPAR Res, 2015, 2015(2): 1-19.
[15]Barger PM, Brandt JM, Leone TC, et al. Deactivation of peroxisome proliferator-activated receptor-α during cardiac hypertrophic growth[J]. J Clin Invest, 2000, 105(12): 1723-1730.
[16]Masamura K, Tanaka N, Yoshida M, et al. Myocardial metabolic regulation through peroxisome proliferator-activated receptor alpha after myocardial infarction[J]. Exp Clin Cardiol, 2003, 8(2): 61-66.
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