基于NF-κB/MAPK通路探讨五味子甲素对心肌缺血再灌注损伤大鼠的保护作用  

Protective Effect of Deoxyschizandrin on Myocardial Ischemia-reperfusion Injury in Rats Based on NF-κB/MAPK Pathway

作　　者：赵志成[1] 刘贵军[1] ZHAO Zhicheng;LIU Guijun(Fourth Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150000,Heilongjiang,China)

机构地区：[1]黑龙江中医药大学附属第四医院,哈尔滨150000

出　　处：《中西医结合心脑血管病杂志》2024年第18期3299-3305,共7页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：黑龙江省中医药科研项目(No.ZHY2022-204)。

摘　　要：目的:探讨五味子甲素(DSD)对心肌缺血再灌注损伤(MIRI)大鼠的保护作用及其对核因子κB(NF-κB)/丝裂原活化蛋白激酶(MAPK)通路的作用机制。方法:将无特定病原体(SPF)组雄性SD大鼠分为假手术组(仅穿线不结扎,生理盐水灌胃)和造模大鼠(MIRI模型)。将造模成功大鼠随机分为模型组(生理盐水灌胃)、阳性药物组(复方丹参滴丸8.5 mg/kg灌胃)、DSD低剂量组(DSD 20 mg/kg灌胃)、DSD中剂量组(DSD 40 mg/kg灌胃)、DSD高剂量组(DSD 80 mg/kg灌胃),每组20只。采用酶联免疫吸附法(ELISA)检测血清肌酸激酶同工酶(CK-MB)、肌红蛋白(Mb)和心肌肌钙蛋白I(cTnI);氯化三苯基四氮唑(TTC)测量心肌梗死面积;苏木精-伊红(HE)染色观察心肌组织病理变化;检测心肌组织丙二醛(MDA)和超氧化物歧化酶(SOD)水平;酶联免疫吸附法(ELISA)检测大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6);蛋白免疫印迹法(Western Blot)检测大鼠心肌组织NF-κB/MAPK通路相关蛋白的表达。结果:与假手术组比较,模型组MIRI大鼠心肌组织肌纤维弯曲,肌细胞减少,肿胀明显,细胞核严重固缩,血清CK-MB、Mb、cTnI水平、心肌梗死面积、心肌细胞凋亡率、MDA、TNF-α、IL-6含量及p-NF-κB p65、磷酸化NF-κB抑制蛋白(p-IκBα)、磷酸化细胞外调节蛋白激酶1/2(p-ERK1/2)、p-p38蛋白水平均升高,SOD活性降低(P<0.05)。与模型组比较,阳性药物组和DSD各剂量组大鼠心肌组织损伤减轻,肌纤维形态完整,肌细胞增加,无明显肿胀,细胞核固缩减轻,血清CK-MB、Mb、cTnI水平、心肌梗死面积、心肌细胞凋亡率、MDA、TNF-α、IL-6含量及p-NF-κB p65、p-IκBα、p-ERK1/2、p-p38蛋白水平均降低,SOD活性升高(P<0.05)。结论:DSD通过抑制NF-κB/MAPK通路,对MIRI大鼠发挥保护作用。Objective:To observe the protective effect of deoxyschizandrin(DSD)on myocardial ischemia-reperfusion injury(MIRI)of rats and its mechanism on nuclear factorκB(NF-κB)/mitogen-activated protein kinase pathway(MAPK)pathway.Methods:Specific pathogen free(SPF)male SD rats were divided into sham group(only threading without ligation,normal saline gavaged)and modeling groups(MIRI model).The rats with successful modeling were randomly divided into model group(normal saline gavaged),positive drug group(compound Dantiorrhiza dripping pills 8.5 mg/kg gavaged),DSD low-dose group(DSD 20 mg/kg gavaged),DSD medium-dose group(DSD 40 mg/kg gavaged)and DSD high-dose group(DSD 80 mg/kg gavaged),with 20 rats in each group.Serum creatine kinase isoenzyme(CK-MB),myoglobin(Mb)and cardiac troponin I(cTnI)were detected by enzyme-linked immunosorbent assay(ELISA).Triphenyltetrazolium chloride(TTC)was used to detect myocardial infarction area.The pathological changes of myocardial tissue were detected by hematoxylin-eosin(HE)staining.The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in myocardial tissue were detected.Serum tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by ELISA.The expression of NF-κB/MAPK pathway-related proteins in rat myocardial tissue was detected by Western Blot.Results:Compared with the sham group,the myocardium of MIRI rats in the model group showed muscle fiber curvature,muscle cell reduction,with obvious swelling,and severe nuclear contraction.Serum CK-MB,Mb,cTnI levels,myocardial infarction area,myocardial cell apoptosis rate,MDA,TNF-α,IL-6 content and p-NF-κB p65,phosphorylated NF-κB inhibitory protein(p-IκBα),phosphorylated extracellular regulatory protein kinase 1/2(p-ERK1/2)and p-p38 were higher,and the SOD activity was lower(P<0.05).Compared with the model group,the myocardial tissue damage of rats in the positive drug group and DSD dose groups was less,the muscle fiber shape was intact,the muscle cells were more without obvious swelling,and the nuclear shrinkage d

关 键 词：心肌缺血再灌注 五味子甲素 核因子κB/丝裂原活化蛋白激酶通路 分子机制 大鼠 实验研究 

分 类 号：R285.5[医药卫生—中药学]