摘要
目的:基于NADPH氧化酶4(Nox4)/蛋白激酶C_(α)(PKC_(α))/半乳糖凝集素3(Gal-3)通路探讨柴胡皂苷D对心肌梗死大鼠心肌纤维化的影响。方法:将SD大鼠随机分为假手术组、模型组、柴胡皂苷D组(50 mg/kg)、Apocynin组(10 mg/kg)、柴胡皂苷D+Apocynin组(柴胡皂苷D 50 mg/kg+Apocynin 10 mg/kg),每组12只。除假手术组外,其余各组制备心肌梗死模型。经药物处理后,采用超声测量各组大鼠心室功能指标左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室射血分数(LVEF)、左室短轴缩短率(LVFS);苏木精-伊红(HE)染色检测各组大鼠心肌组织形态;Masson染色检测各组大鼠心肌组织纤维化改变,并计算心肌组织胶原容积积分(CVF);酶联免疫吸附法(ELISA)检测各组大鼠血清白细胞介素(IL)-1β、IL-6、转化生长因子(TGF)-β_(1)水平;蛋白免疫印迹法(Western Blot)检测各组大鼠心肌组织Nox4/PKC_(α)/Gal-3通路相关蛋白表达含量。结果:相较于假手术组,模型组大鼠心肌组织有严重的病理损伤,胶原增生明显,心肌CVF、LVEDD、LVESD及血清IL-1β、IL-6、TGF-β_(1)水平升高,心肌组织Nox4、PKC_(α)及Gal-3蛋白表达升高(P<0.05),LVEF及LVFS降低(P<0.05)。相较于模型组,各药物组大鼠心肌组织病理损伤减轻,胶原增生减少,CVF、LVEDD、LVESD及血清IL-1β、IL-6、TGF-β_(1)水平降低,心肌组织Nox4、PKC_(α)及Gal-3蛋白表达降低(P<0.05),LVEF及LVFS升高(P<0.05)。相较于柴胡皂苷D组、Apocynin组,柴胡皂苷D+Apocynin组大鼠心肌组织病理损伤进一步减轻,且胶原增生进一步减少,CVF、LVEDD、LVESDE及血清IL-1β、IL-6、TGF-β_(1)水平降低,心肌组织Nox4、PKC_(α)及Gal-3蛋白表达降低(P<0.05),LVEF及LVFS升高(P<0.05)。结论:柴胡皂苷D可抑制Nox4/PKC_(α)/Gal-3通路激活,减轻心肌梗死大鼠心肌组织炎症损伤,缓解心肌纤维化,改善心功能。
Objective:To observe the effect of saikosaponin D on myocardial fibrosis in rats with myocardial infarction based on the NADPH oxidase 4(Nox4)/protein kinase C_(α)(PKC_(α))/galactose lectin 3(Gal-3)pathway.Methods:The SD rats were randomly divided into the sham group,model group,saikosaponin D group(50 mg/kg of saikosaponin D),Apocynin group(10 mg/kg of Apocynin),and saikosaponin D+Apocynin group(50 mg/kg of saikosaponin D and 10 mg/kg of Apocynin),with 12 rats in each group.Myocardial infarction model was prepared in all groups except sham group.After drug treatment,left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),and left ventricular short-axis shortening rate(LVFS)were detected by ultrasonography.Hematoxylin-eosin(HE)staining was used to detect myocardial tissue morphology in each group.Masson staining was used to detect myocardial fibrosis,and myocardial collagen volume integral(CVF)was calculated.Serum levels of interleukin(IL)-1β,IL-6 and transforming growth factor(TGF)-β_(1) were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of Nox4/PKC_(α)/Gal-3 pathway-related protein in myocardium of rats in each group were detected by Western Blot.Results:Compared with sham group,myocardial tissue in the model group showed serious pathological injury,and obvious collagen hyperplasia,CVF,LVEDD and LVESD,serum levels of IL-1β,IL-6 and TGF-β_(1),myocardial tissue Nox4,PKC_(α)and Gal-3 protein expression increased(P<0.05),LVEF and LVFS decreased(P<0.05).Compared with the model group,pathological injury of myocardial tissue and collagen hyperplasia reduced,CVF,LVEDD and LVESD,serum levels of IL-1β,IL-6 and TGF-β_(1),myocardial Nox4,PKC_(α)and Gal-3 protein expression decreased in all drug groups(P<0.05),LVEF and LVFS were increased(P<0.05).Compared with the saikosaponin D group and Apocynin group,pathological injury of myocardial tissue and collagen hyperplasia further reduced,CVF,LVEDD and LVESD,serum leve
作者
李耀征
白保强
孙亚勤
王贺
LI Yaozheng;BAI Baoqiang;SUN Yaqin;WANG He(Zhumadian Central Hospital,Zhumadian 463000,Henan,China)
出处
《中西医结合心脑血管病杂志》
2023年第20期3724-3729,共6页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
2019年河南省中医药科学研究专项课题(No.2019ZY2139)。
