促红细胞生成素衍生肽对急性心肌梗死大鼠心脏的保护作用
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摘要
目的探讨促红细胞生成素衍生肽(helix B surface peptide,HBSP)对急性心肌梗死(acute myocardial infarction,AMI)大鼠心脏的保护作用。方法将30只8周龄SD雄性大鼠随机分3组:假手术组(sham组)、AMI组和HBSP组,每组10只。采用结扎大鼠冠状动脉前降支术以构建AMI大鼠模型,治疗组为术后予腹腔注射HBSP(90μg/kg);假手术组和AMI组给予等量生理盐水腹腔注射。术后24 h心脏彩超检测心功能,处理各组大鼠,以蛋白免疫印迹法检测心肌组织信号传导与转录激活因子3(signal transduction and transcription activator 3,STAT3)、B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)、Bax蛋白(BCL2 associated X protein)表达,原位缺口末端标记法(TUNEL法)检测心肌细胞凋亡情况。结果 HBSP治疗组与AMI组比较,大鼠心肌梗死面积及心功能明显改善。AMI组与假手术组比较,STAT3、Bcl-2表达明显下降而Bax表达显著上升(P<0.01),HBSP组STAT3、Bcl-2表达较AMI组显著升高,而Bax表达显著减少(P<0.01)。与假手术组比较,AMI组心肌细胞凋亡率明显增加(P<0.01),而HBSP组心肌细胞凋亡率明显降低(P<0.01)。AMI模型组心功能指标显著低于假手术组(P<0.01),而HBSP治疗组心功能指标明显高于AMI模型组(P<0.01)。结论 HBSP可使STAT3、Bcl-2表达增加抑制急性心肌梗死大鼠心肌细胞凋亡,从而保护心肌组织,改善大鼠心功能。
Objective To investigate the protective effect of helix B surface peptide(HBSP) on the heart of rats with acute myocardial infarction(AMI). Methods Thirty 8-week-old male SD rats were randomly divided into 3 groups: sham operation group(sham group), AMI group and HBSP group. The AMI rat model was established by ligating the anterior descending coronary artery. The treatment group was intraperitoneally injected with HBSP(90 μg/kg), the sham operation group and AMI group were intraperitoneally injected with the same amount of normal saline. Cardiac function was detected by color Doppler echocardiography 24 hours after operation. The myocardial signal transduction and transcription activator 3(STAT3), B lymphocytoma 2 gene(Bcl-2) were detected by Western blotting in each group of rats. Apoptosis was detected by expression of Bcl-2, Bax protein(BCL2 associated X protein) and detection of myocardial fineness by in situ Nick end labeling(TUNEL). Results Compared with AMI group, myocardial infarction size and cardiac function of rats in HBSP group were significantly improved. STAT3, Bcl-2 expression in AMI group was significantly lower than that in sham operation group(P<0.01). In HBSP group, STAT3 was significantly higher than that in sham operation group(P<0.01). In HBSP group, the expression of Bcl-2 was significantly higher than that of AMI, while the expression of Bax was significantly decreased(P<0.01). Compared with the sham operation group, the cardiomyocyte apoptosis rate in the AMI group was significantly increased, while that in the HBSP group was significantly lower than that in the sham operation group(P<0.01). AMI model group was significantly lower than that in the sham operation group. The cardiac function in HBSP group was significantly higher than that in AMI model group(P<0.01). Conclusion HBSP can increase the expression of STAT3, Bcl-2 and inhibit the apoptosis of myocardial cells in rats with acute myocardial infarction, thereby protecting myocardial tissue and improving cardiac function in rats.
Objective To investigate the protective effect of helix B surface peptide(HBSP) on the heart of rats with acute myocardial infarction(AMI). Methods Thirty 8-week-old male SD rats were randomly divided into 3 groups: sham operation group(sham group), AMI group and HBSP group. The AMI rat model was established by ligating the anterior descending coronary artery. The treatment group was intraperitoneally injected with HBSP(90 μg/kg), the sham operation group and AMI group were intraperitoneally injected with the same amount of normal saline. Cardiac function was detected by color Doppler echocardiography 24 hours after operation. The myocardial signal transduction and transcription activator 3(STAT3), B lymphocytoma 2 gene(Bcl-2) were detected by Western blotting in each group of rats. Apoptosis was detected by expression of Bcl-2, Bax protein(BCL2 associated X protein) and detection of myocardial fineness by in situ Nick end labeling(TUNEL). Results Compared with AMI group, myocardial infarction size and cardiac function of rats in HBSP group were significantly improved. STAT3, Bcl-2 expression in AMI group was significantly lower than that in sham operation group(P<0.01). In HBSP group, STAT3 was significantly higher than that in sham operation group(P<0.01). In HBSP group, the expression of Bcl-2 was significantly higher than that of AMI, while the expression of Bax was significantly decreased(P<0.01). Compared with the sham operation group, the cardiomyocyte apoptosis rate in the AMI group was significantly increased, while that in the HBSP group was significantly lower than that in the sham operation group(P<0.01). AMI model group was significantly lower than that in the sham operation group. The cardiac function in HBSP group was significantly higher than that in AMI model group(P<0.01). Conclusion HBSP can increase the expression of STAT3, Bcl-2 and inhibit the apoptosis of myocardial cells in rats with acute myocardial infarction, thereby protecting myocardial tissue and improving cardiac function in rats.
引文
[1] 卢芬萍,苏宁,征宗梅,等.促红细胞生成素对急性心肌梗死经皮冠状动脉成形术后疗效的Meta分析及系统评价[J].中国动脉硬化杂志,2018,26(1):77-84.
[2] 韦杨,秦俭.促红细胞生成素在慢性心力衰竭中的应用进展[J].心血管病学进展,2017,38(3):285-288.
[3] 吴婷婷,丁晶,汪昕.新型促红细胞生成素衍生肽的制备[J].中国临床神经科学,2018,26(3):256-261.
[4] ZHANG C,YANG C,ZHU T.From erythropoietin to its peptide derivatives:smaller but stronger[J].Curr Protein Pept Sci,2017,18(12):1191-1194.
[5] POCHHI M,MUDDESHWAR M G.Serum enzymes markers in myocardial infarction:a study of rural area[J].Asi J Med Sci,2017,8(2):34.
[6] 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):996-999.
[7] 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):111-119.
[8] 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):1122-1124.
[9] WU S,YANG C,XU N,et al.The protective effects of helix b surface peptide on experimental acute liver injury induced by carbon tetrachloride[J].Dig Dis Sci,2017,62(6):1537-1549.
[10] 刘超权,司瑞,宁明安,等.促红细胞生成素衍生肽抑制细胞自噬减轻小鼠心肌缺血/再灌注损伤[J].心脏杂志,2016,28(4):390-395.
[11] 林洁,吴广文,付长龙,等.大鼠电针后血清对肿瘤坏死因子α诱导凋亡软骨细胞Erk1/2、C-Myc、C-Fos和C-Jun基因表达的影响[J].福建中医药,2018,49(2):20-23.
[12] 李鹏飞.血清外泌体通过ERK1/2发挥抵抗H2O2诱导的大鼠心肌细胞凋亡的作用[D].南京:南京医科大学,2018.
[13] 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):938-942.
[14] LIU P,YOU W,LIN L,et al.Helix B surface peptide protects against acute myocardial ischemia-reperfusion injury via the RISK and SAFE pathways in a mouse model[J].Cardiology,2016,134(2):109-117.
[15] 叶敏,刘志强,王李俊,等.猪苓酮A通过调节Bcl-2/Bax信号通路诱导雌激素受体阴性的乳腺癌细胞凋亡研究[J].中草药,2018,49(22):5334-5338.
[2] 韦杨,秦俭.促红细胞生成素在慢性心力衰竭中的应用进展[J].心血管病学进展,2017,38(3):285-288.
[3] 吴婷婷,丁晶,汪昕.新型促红细胞生成素衍生肽的制备[J].中国临床神经科学,2018,26(3):256-261.
[4] ZHANG C,YANG C,ZHU T.From erythropoietin to its peptide derivatives:smaller but stronger[J].Curr Protein Pept Sci,2017,18(12):1191-1194.
[5] POCHHI M,MUDDESHWAR M G.Serum enzymes markers in myocardial infarction:a study of rural area[J].Asi J Med Sci,2017,8(2):34.
[6] 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):996-999.
[7] 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):111-119.
[8] 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):1122-1124.
[9] WU S,YANG C,XU N,et al.The protective effects of helix b surface peptide on experimental acute liver injury induced by carbon tetrachloride[J].Dig Dis Sci,2017,62(6):1537-1549.
[10] 刘超权,司瑞,宁明安,等.促红细胞生成素衍生肽抑制细胞自噬减轻小鼠心肌缺血/再灌注损伤[J].心脏杂志,2016,28(4):390-395.
[11] 林洁,吴广文,付长龙,等.大鼠电针后血清对肿瘤坏死因子α诱导凋亡软骨细胞Erk1/2、C-Myc、C-Fos和C-Jun基因表达的影响[J].福建中医药,2018,49(2):20-23.
[12] 李鹏飞.血清外泌体通过ERK1/2发挥抵抗H2O2诱导的大鼠心肌细胞凋亡的作用[D].南京:南京医科大学,2018.
[13] 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):938-942.
[14] LIU P,YOU W,LIN L,et al.Helix B surface peptide protects against acute myocardial ischemia-reperfusion injury via the RISK and SAFE pathways in a mouse model[J].Cardiology,2016,134(2):109-117.
[15] 叶敏,刘志强,王李俊,等.猪苓酮A通过调节Bcl-2/Bax信号通路诱导雌激素受体阴性的乳腺癌细胞凋亡研究[J].中草药,2018,49(22):5334-5338.