摘要
目的探讨白芷乙素通过抑制细胞外信号调节激酶1/2(ERK1/2)和核转录因子-κB (NF-kappaB p65)的活化,减轻心肌缺血再灌注(MI/R)大鼠心肌损伤和氧化应激的作用机制。方法将SD大鼠随机分为五组:健康对照组(Control组),心肌缺血再灌注模型组(MI/R组),低、中、高剂量白芷乙素组(6.25、12.50、25.00 mg/kg)。小动物超声仪检测大鼠心率(HR)、左心室缩短分数(FS);酶联免疫吸附法(ELISA)检测心脏损伤指标肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白(cTnI)水平;HE染色观察心肌组织损伤情况;末端脱氧核苷酸转移酶介导的dUTP镍端标记(TUNEL)检测心肌细胞凋亡情况;Western blot检测凋亡相关蛋白Bax、Bcl-2和caspase-3及通路蛋白ERK1/2和p65的表达情况;试剂盒检测超氧化物歧化酶(SOD)活性和丙二醇(MDA)含量。结果与Control组比较,MI/R组的HR、FS降低(P<0.05);CK-MB和cTnI浓度升高(P<0.05);心肌组织损伤严重;凋亡细胞及Bax/Bcl-2表达比值增加(P<0.05);SOD活性降低(P<0.05),而MDA含量升高(P<0.05);ERK1/2和p65蛋白磷酸化升高(P<0.05)。白芷乙素给药后,逆转了MI/R大鼠的上述结果。与MI/R组比较,中、高剂量白芷乙素组的HR、FS回升(P<0.05);CK-MB和cTnI浓度回降(P<0.05);心肌组织损伤改善;凋亡细胞及Bax/Bcl-2表达比值回降(P<0.05);SOD活性回升(P<0.05),而MDA含量回降(P<0.05);ERK1/2和p65蛋白磷酸化回降(P<0.05)。结论白芷乙素可通过抑制ERK1/2和NF-κBp65通路蛋白活化,缓解MI/R大鼠心肌损伤及氧化应激。
Objective This study aims to investigate the effects of imperatorin on myocardial injury and oxidative stress in myocardial ischemia-reperfusion rats by inhibiting the activation of extracellular signal-regulated kinase 1/2(ERK1/2)and Nuclear factor-kappaB phosphorylation-65(NF-kappaB p65).Methods SD rats were randomly divided into five groups:healthy Control group(Control group),myocardial ischemia-reperfusion model group(MI/R group),and low,medium and high doses of imperatorin 6.25,12.5 and 25 mg/kg groups.The rat heart rate(HR) and left ventricular shortening fraction score(FS) were detected by small animal ultrasound instrument.Enzyme-linked immunosorbent assay(ELISA) was used to detect creatine kinase-MB(CK-MB)and Cardiac troponin I(cTnI).Myocardial tissue damage was observed by HE staining.Terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labelling(TUNEL) was used to detect the apoptosis of cardiomyocytes.The expression of apoptosis-related proteins Bax,Bcl-2,Caspase-3 and pathway proteins ERK1/2 and NF-κB p65 were detected by Western blot. Superoxide dismutase( SOD) activity and Malondialdehyde( MDA) content were detected by the kit.Results Compared with the control group,HR and FS in MI/R group significantly reduced( P < 0. 05);CK-MB and cTnI concentrations increased significantly( P < 0. 05);myocardial tissue damage was obvious;apoptotic cells and Bax/Bcl-2 expression ratio significantly increased( P < 0. 05);SOD activity significantly decreased( P <0. 05),while MDA content significantly increased( P < 0. 05);phosphorylation of ERK1/2 and NF-κB p65 significantly increased( P < 0. 05). The above results were reversed in MI/R rats after administration of imperatorin. Compared with the MI/R group,the HR and FS of the medium and high doses imperatorin groups were significantly recovered( P < 0. 05);the concentration of CK-MB and cTnI decreased significantly( P < 0. 05);myocardial tissue injury improved obviously;apoptotic cells and Bax/Bcl-2 expression ratio decreased significantly( P < 0. 05);SOD activity significantly increased( P < 0. 05),while MDA content significantly decreased( P < 0. 05);phosphorylation of ERK1/2 and NF-κB p65 decreased significantly( P < 0. 05). Conclusion Imperatorin can alleviate myocardial injury and oxidative stress in MI/R rats by inhibiting the activation of ERK1/2 and NF-κB p65 pathway proteins.
作者
黎明
王妹芳
吴宝珍
刘珍君
李波
姚峰
Li Ming;Wang Meifang;Wu Baozhen(Dept of Cardiovascular Medicine,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524000)
出处
《安徽医科大学学报》
CAS
北大核心
2021年第2期249-255,共7页
Acta Universitatis Medicinalis Anhui
基金
广东省医学科研基金(编号:A2019089)。
作者简介
黎明,男,主治医师;责任作者:姚峰,男,主治医师,E-mail:yaofeng0704@126.com。
