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郭正亮,俞许超,周宇,赵敬平,金雪梅,赵辉.白杨素通过下调P38-MAPK磷酸化减轻脓毒症大鼠的心肌损伤[J].浙江中西医结合杂志,2021,31(3):
白杨素通过下调P38-MAPK磷酸化减轻脓毒症大鼠的心肌损伤
Chrysin attenuates myocardial injury in septic rats by down regulating p38-MAPK phosphorylation
投稿时间:2020-08-26  修订日期:2021-03-04
DOI:
中文关键词:  白杨素  P38-MAPK  磷酸化  脓毒症  心肌损伤
英文关键词:Chrysin  p38-MAPK  Phosphorylation  Sepsis  Myocardial injury
基金项目:
作者单位E-mail
郭正亮 诸暨市人民医院 taoxikai1984@163.com 
俞许超 诸暨市人民医院  
周宇 诸暨市人民医院  
赵敬平 诸暨市人民医院  
金雪梅* 诸暨市人民医院  
赵辉 温州医科大学附属第一医院  
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中文摘要:
      目的 探讨白杨素通过下调P38-有丝分裂原激活的蛋白激酶(MAPK)磷酸化减轻脓毒症大鼠心肌损伤的机制。方法 清洁级SD大鼠100只,随机分成:对照组、模型组、地塞米松组(0.27 mg?kg-1)、白杨素低剂量组(20 mg?kg-1)、白杨素高剂量组(40 mg?kg-1),每组20只。模型组、地塞米松组、白杨素低、高剂量组建立脓毒症模型;建模成功后,地塞米松组、白杨素低、高剂量组给予相应药物灌胃,对照组及模型组给予等体积的生理盐水,连续给药4周。试验结束后,测定大鼠心功能指标,苏木精-伊红(HE)染色观察大鼠心肌组织病理学变化,实时荧光定量PCR(qRT-PCR)及蛋白免疫印迹(western blot)法测定大鼠心肌P38、磷酸化MAPK(p-MAPK)mRNA和蛋白水平。结果 与对照组比较,模型组大鼠左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)水平、P38、p-MAPK mRNA和蛋白水平升高,短轴缩短分数(FS)、射血分数(EF)水平降低(P<0.05);与模型组比较,地塞米松组、白杨素低剂量组、白杨素高剂量组LVEDD、LVESD水平、P38、p-MAPK mRNA和蛋白水平降低,FS、EF水平升高(P<0.05);与地塞米松组比较,白杨素低剂量组LVEDD、LVESD水平、P38、p-MAPK mRNA和蛋白水平升高,FS、EF水平降低(P<0.05);白杨素高剂量组LVEDD、LVESD、FS、EF水平、P38、p-MAPK mRNA和蛋白水平与地塞米松组比较无明显差异(P>0.05)。结论 白杨素能够减轻脓毒症大鼠的心肌损伤,减轻心肌细胞炎症反应;其机制可能与白杨素可显著抑制脓毒症大鼠心肌细胞P38-MAPK磷酸化有关。
英文摘要:
      Objective: To investigate the effect of chrysin on myocardial injury in sepsis rats by down regulating p38-mitogen activated protein kinase(MAPK) phosphorylation. Methods: 100 SD rats of clean grade were randomly divided into control group, model group, dexamethasone group (0.27 mg?kg-1), low-dose chrysin group (20 mg?kg-1) and high-dose chrysin group (40 mg?kg-1), 20 in each group. The rats in the model group, dexamethasone group, low and high dose groups of chrysin were used to establish sepsis model. After the model was established successfully, the rats in the dexamethasone group, low and high dose groups of chrysin were given corresponding drugs by gavage, control group and model group were given equal volume of normal saline. Continuous administration for 4 weeks. At the end of the experiment, the indexes of cardiac function were measured, HE staining was used to observe the pathological changes of myocardium in rats, The mRNA and protein levels of p38 and phosphorylated MAPK(p-MAPK) were measured by quantitative real-time PCR(qRT-PCR) and western blot. Results: Compared with the control group, the level of left ventricular end diastolic diameter(LVEDD), left ventricular end systolic diameter(LVESD), p38, p-MAPK mRNA and protein in the model group were significantly increased, while the level of fractional shortening(FS) and ejection fraction(EF) were significantly decreased(P<0.05). Compared with the model group, the level of LVEDD, LVESD, p38, p-MAPK mRNA and protein in the dexamethasone group, the low-dose group of chrysin, the high-dose group of chrysin were significantly decreased, and the level of FS and EF were significantly increased(P<0.05). Compared with dexamethasone group, the levels of LVEDD, LVESD p38, p-MAPK mRNA and protein levels in the low-dose group were significantly increased, while FS and EF levels were significantly decreased(P<0.05). There was no significant difference in LVEDD, LVESD, FS, EF, P38 and p-MAPK mRNA and protein between dexamethasone group and the high-dose group of chrysin(P>0.05). Conclusion: Chrysin can alleviate myocardial injury and reduce myocardial inflammatory response in septic rats. Its mechanism may be related to the inhibition of P38-MAPK phosphorylation in cardiomyocytes of septic rats.
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