促红细胞生成素衍生肽对急性心肌梗死大鼠炎症和Erk1/2表达的影响
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摘要
目的探讨促红细胞生成素衍生肽(HBSP)对急性心肌梗死(AMI)大鼠心脏炎症的影响和机制。方法将30只8周龄SD雄性大鼠随机分为3组:假手术组(sham组)、AMI组和HBSP组。采用结扎大鼠冠状动脉前降支术以构建AMI大鼠模型,HBSP组为术后予腹腔注射HBSP(90μg/kg);sham组和AMI组予等量生理盐水腹腔注射。大鼠处死前心脏彩超检测心功能,处理各组大鼠,检测心肌组织白介素6(IL-6)、肿瘤坏死因子α(TNF-α)、磷酸化细胞外信号调节激酶1/2(p-Erk1/2)和细胞外调节蛋白激酶1/2(Erk1/2)蛋白表达。结果与sham组比较,AMI组心肌组织IL-6、TNF-α、p-Erk1/2和Erk1/2蛋白表达明显升高(P=0.001);而HBSP组大鼠心肌组织IL-6、TNF-α、p-Erk1/2和Erk1/2蛋白表达显著减少(P=0.001)。AMI模型组心功能指标显著低于sham组,而HBSP治疗组心功能指标明显高于AMI模型组(P=0.001)。结论 HBSP可减轻心肌梗死炎症和心肌损伤,抑制Erk1/2信号通路,从而保护心肌组织,改善大鼠心功能。
Objective To investigate the effect and mechanism of erythropoietin derived peptide(HBSP) on cardiac inflammation in rats with acute myocardial infarction(AMI). Methods Thirty 8 week old SD male rats were randomly divided into 3 groups(sham operation group, operation group and HBSP group). The AMI rat model was established by ligating the anterior descending coronary artery. The HBSP(90 μg/kg) was injected intraperitoneally in the AMI group, and the sham operation group and the AMI group were intraperitoneally injected with the same amount of normal saline. Cardiac function was detected by color Doppler echocardiography before the rats were killed. The expression of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), p-Erk 1/2 and Erk1/2 protein were detected in each group. Results Compared with sham group, the expression of IL-6,TNF-α, p-Erk1/2 and Erk1/2 protein in myocardial tissue of AMI group was significantly increased(P=0.001), while that of IL-6,TNF-α, p-Erk1/2 and Erk1/2 protein in myocardial tissue of HBSP group was significantly decreased(P=0.001). The cardiac function index of AMI model group was significantly lower than that of sham group, while that of HBSP treatment group was significantly higher than that of AMI model group(P=0.001). Conclusion HBSP can attenuate myocardial infarction inflammation and myocardial damage by inhibiting Erk1/2 signaling pathway, thereby protecting myocardial tissue and improving cardiac function in rats.
Objective To investigate the effect and mechanism of erythropoietin derived peptide(HBSP) on cardiac inflammation in rats with acute myocardial infarction(AMI). Methods Thirty 8 week old SD male rats were randomly divided into 3 groups(sham operation group, operation group and HBSP group). The AMI rat model was established by ligating the anterior descending coronary artery. The HBSP(90 μg/kg) was injected intraperitoneally in the AMI group, and the sham operation group and the AMI group were intraperitoneally injected with the same amount of normal saline. Cardiac function was detected by color Doppler echocardiography before the rats were killed. The expression of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), p-Erk 1/2 and Erk1/2 protein were detected in each group. Results Compared with sham group, the expression of IL-6,TNF-α, p-Erk1/2 and Erk1/2 protein in myocardial tissue of AMI group was significantly increased(P=0.001), while that of IL-6,TNF-α, p-Erk1/2 and Erk1/2 protein in myocardial tissue of HBSP group was significantly decreased(P=0.001). The cardiac function index of AMI model group was significantly lower than that of sham group, while that of HBSP treatment group was significantly higher than that of AMI model group(P=0.001). Conclusion HBSP can attenuate myocardial infarction inflammation and myocardial damage by inhibiting Erk1/2 signaling pathway, thereby protecting myocardial tissue and improving cardiac function in rats.
引文
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[15] Wei N,Zhang C,He H,et al.Protective effect of saponins extract from Panax japonicus on myocardial infarction:involvement of NF-κB,Sirt1 and mitogen-activated protein kinase signalling pathways and inhibition of inflammation[M].J Pham Phamacol,2014,66(11):1641-51.
[16] 王菁,徐美林,畅昶,等.ERK1/2信号转导通路参与冠心病致心肌炎症的机制[J].天津医药,2016,44(8):938-42.
[2] Unden J,Sjolund C,Lansberg J K,et al.Post-ischemic continuous infusion of erythropoeitin enhances recovery of lost memory function after global cerebral ischemia in the rat[J].BMC Neurosci,2013,14:27.
[3] Ferrario M,Arbustini E,Massa M,et al.High-dose erythropoietin in patients with acute myocardial infarction:a pilot,randomised,placebo-controlled study[J].Int J Cardiol,2011,147(1):124-31.
[4] Yang C,Zhao T,Lin M,et al.Helix B surface peptide administered after insult of ischemia reperfusion improved renal function,structure and apoptosis through beta common receptor/erythropoietin receptor and PI3K/Akt pathway in a murine model[J].Exp Biol Med,2013,238(1):111-9.
[5] 游伟,刘映峰,缪绯,等.促红细胞生成素衍生肽对小鼠心肌缺血再灌注损伤的作用及机制研究[J].中国循环杂志,2015,30(10):996-9.
[6] Zhang C,Yang C,Zhu T.From erythropoietin to its peptide derivatives:smaller but stronger[J].Curr Protein Pept Sci,2017,18(12):1191-4.
[7] 游伟,刘映峰,缪绯,等.促红细胞生成素衍生肽的组织保护作用研究进展[J].中国循环杂志,2015,30(11):1122-4.
[8] Lu X,Bijli K M,Ramirez A,et al.Hypoxia downregulates PPARγ via an ERK1/2-NF-κB-Nox4-dependent mechanism in human pulmonary artery smooth muscle cells[J].Free Radic Biol Med,2013,63:151-60.
[9] Li L,Li D H,Qu N,et al.The role of ERK1/2 signaling pathway in coronary microembolization-induced rat myocardial inflammation and injury[J].Cardiology,2011,117(3):207-15.
[10] Martin P.Long-term extracellular signal-related kinase activation following cadmium intoxication is negatively regulated by a protein kinase C-dependent pathway affecting cadmium transport[J].FEBS J,2009,276(6):1667-79.
[11] Armstrong S C.Protein kinase activation and myocardial ischemia/reperfusion injury[J].Cardiovascular Res,2004,61(3):427-36.
[12] Weifeng L,Huimin H,Yanmin Z,et al.Anti-inflammatory effect of tetrahydrocoptisine from Corydalis impatiens is a function of possible inhibition of TNF-α,IL-6 and NO production in lipopolysaccharide-stimulated peritoneal macrophages through inhibiting NF-κB activation and MAPK pathway[J].Eur J Pharmacol,2013,715(1-3):62-71.
[13] Oh W J,Jung U,Eom H S,et al.Inhibition of lipopolysaccharide-induced proinflammatory responses by Buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-kB and ERK1/2 signaling[J].Molecules,2013,18(8):9195-206.
[14] Abarikwu S O.Kolaviron,a natural flavonoid from the seeds of Garcinia kola ,reduces LPS-induced inflammation in macrophages by combined inhibition of IL-6 secretion,and inflammatory transcription factors,ERK1/2,NF-κB,p38,Akt,p-c-JUN and JNK[J].Biochim Biophys Acta,2014,1840(7):2373-81.
[15] Wei N,Zhang C,He H,et al.Protective effect of saponins extract from Panax japonicus on myocardial infarction:involvement of NF-κB,Sirt1 and mitogen-activated protein kinase signalling pathways and inhibition of inflammation[M].J Pham Phamacol,2014,66(11):1641-51.
[16] 王菁,徐美林,畅昶,等.ERK1/2信号转导通路参与冠心病致心肌炎症的机制[J].天津医药,2016,44(8):938-42.