蛋白激酶D1调控胶原表达逆转心肌梗死后心室重构的作用  

Protein kinase D1 reverses ventricular remodeling after myocardial infarction through modulating collagen expression

作　　者：杨雷[1] 刘暖[1] 毛秉豫[1] Yang Lei;Liu Nuan;Mao Bingyu(Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation,Nanyang Institute of Technology,Nanyang 473004)

机构地区：[1]南阳理工学院河南省张仲景方药与免疫调节重点实验室

出　　处：《安徽医科大学学报》2019年第10期1535-1539,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81873106、81473438、81202791)

摘　　要：目的探讨蛋白激酶D1(PKD1)是否通过调控胶原表达逆转心肌梗死(MI)后心室重构(VR)的作用。方法应用雄性Wistar大鼠,按照数字随机法分为3组:假手术组、模型组和PKD1组,每组大鼠均15只。模型组和PKD1组采用经典的左冠状动脉结扎术复制MI模型,假手术组仅履行手术程序但不结扎冠状动脉。PKD1组给予每日1 mg/(kg d)的剂量灌胃给药,假手术组和模型组给予等量生理盐水。4周后进行血流动力学评估,并应用HE染色、心肌细胞横截面面积测定、Masson染色、Western blot等方法分析PKD1对心肌组织肥大程度的影响和对胶原蛋白表达的调控作用。结果与模型组比较,PKD1用药可改善MI后心肌组织的血流动力指标和心肌组织的坏死程度,降低心肌细胞的横截面面积和心肌组织的胶原占比,上调心肌组织中基质金属蛋白酶抑制剂1(TIMP1)的表达,下调基质金属蛋白酶1(MMP-1)、MMP-8、Ⅰ型胶原(ColⅠ)、ColⅢ、前胶原C端蛋白酶增强子(PCPE)、富含半胱氨酸的分泌型酸性蛋白(SPARC)、大鼠粘胶蛋白/肌腱蛋白(TN-C)和核转录因子(NF-κB)p50的表达,差异均有统计学意义(P<0.01)。结论PKD1可能有调控心肌组织中的胶原表达而逆转MI后VR的作用。Objective To determine whether protein kinase D1(PKD1)would reverse ventricular remodeling after myocardial infarction(MI)through modulating collagen expression.Methods Male Wistar rats were randomly divided into three groups:sham group,model group and PKD1 group,number of rats was 15 in each group.MI was induced in rats by ligation of the left anterior descending coronary artery(LAD),while sham surgery without LAD ligation.PKD1 group was given PKD1 by 1 mg/(kg d)after oral administration,while the sham and model groups were fed the same equivalent normal saline.After 4 weeks,hemodynamic characteristics were obtained by a pressure-volume catheter,and HE staining,the histologic analysis of myocyte cross-sectional area,the Masson staining and the Western blot method were implemented to assess the effect of PKD1 on the hypertrophy and expression of collagen proteins.Results Compared with the model group,PKD1 significantly improved the hemodynamic parameters and the degree of myocardial necrosis after MI,decreased the cross-sectional area of myocardial cells and collagen percentage of myocardial tissue,up-regulated the protein expression of matrix metalloproteinase inhibitors 1(TIMP1),and down-regulated the expression of matrix metalloproteinase-1(MMP-1),MMP-8,collagen typeⅠ(ColⅠ),ColⅢ,procollagen C-terminal protease enhancer(PCPE),secreted protein acidic and rich in cysteine(SPARC),Tenascin-C(TN-C)and nuclear factor kappa B(NF-κB)p50,while the difference was statistically significant(P<0.01).Conclusion Protein kinase D1 might reverse the ventricular remodeling after MI through regulation of the collagen expression in myocardium.

关 键 词：蛋白激酶D1 心肌梗死 胶原表达 心室重构 心肌肥大 

分 类 号：R392.31[医药卫生—免疫学] R361.1[医药卫生—基础医学]