螺内酯通过抑制左心室肥厚大鼠促肥大生长因子的表达和c-Raf/ERK1/2信号通路的活化来预防左心室肥厚  

Spironolactone prevents left ventricular hypertrophy by inhibiting expression of mast growth factor and activation of c-Raf/ERK1/2 signaling pathway in rats with left ventricular hypertrophy

作　　者：刘红 张维新 张玲燕 LIU Hong;ZHANG Wei-Xin;ZHANG Ling-Yan(Department of Cardiovascular Medicine,Henan Zhengzhou Hospital of Traditional Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南省郑州市中医院内五科

出　　处：《中国免疫学杂志》2019年第20期2464-2469,共6页Chinese Journal of Immunology

摘　　要：目的:探讨螺内酯对左心室肥厚大鼠免疫及炎症的干预作用及机制。方法:采用腹主动脉缩窄法建立压力超负荷诱导的左心室肥厚大鼠模型,每天按照20 mg/kg的剂量对螺内酯组的左心室肥厚模型大鼠灌胃螺内酯,对照组、模型组和假手术组大鼠灌胃等体积的生理盐水,共治疗8周。采用Sircol Soluble Collagen Assay胶原蛋白检测试剂盒测定大鼠左心室匀浆中的总可溶性胶原。采用ELISA法检测心室组织匀浆中的PDGF-BB和TGF-β1水平,采用qPCR检测c-myc、GATA4和ANP的表达,采用Western blot检测大鼠左心室组织中c-Raf和ERK1/2的活化情况。结果:模型组大鼠的左心室重量与体重比值(VW/BW)比对照组显著增加了36.60%,而螺内酯可显著降低大鼠的VW/BW。模型组大鼠心室总胶原蛋白相对表达量显著上调了46.45%,而螺内酯组与对照组无显著差异。模型组大鼠的PDGF-BB和TGF-β1表达量分别显著上调了70.14%和118.47%,螺内酯组显著低于模型组,且与对照组无显著差异。模型组大鼠的c-Raf和ERK1/2磷酸化水平分别显著上调了106.25%和74.00%,而螺内酯组与对照组无显著差异。模型组大鼠的c-myc和GATA4 mRNA表达水平分别显著上调了115.01%和254.00%,而螺内酯处理可抑制c-myc和GATA4 mRNA的上调。模型组大鼠的ANP mRNA表达水平显著上调了421.00%,而螺内酯处理可抑制ANP mRNA的上调。结论:螺内酯通过抑制了促肥大生长因子(PDGF-BB和TGF-β1)的表达和c-Raf/ERK1/2信号通路的活化来预防左心室肥厚。Objective:To investigate the intervention and mechanism of spironolactone on immunity and inflammation in rats with left ventricular hypertrophy.Methods: A rat model of left ventricular hypertrophy induced by pressure overload was established by abdominal aortic coarctation.The left ventricular hypertrophy model rats in the spironolactone group were given spironolactone daily at a dose of 20 mg/kg.The rats in the control group,the model group and the sham-operated group were given saline of equal volume by gavage for 8 weeks.Total soluble collagen in rat left ventricular homogenate was determined using the Sircol Soluble Collagen Assay Collagen Assay Kit.The levels of PDGF-BB and TGF-β1 in ventricular tissue homogenate were detected by ELISA.The expressions of c-myc,GATA4 and ANP were detected by RT-qPCR.The c-Raf and ERK1/2 activation conditions in left ventricular tissue were detected by Western blot.Results: The VW/BW ratio of the model group was significantly increased by 36.60% compared with the control group,while spironolactone significantly decreased the ratio of left ventricular weight to body weight(VW/BW) of the rats.The relative expression of total collagen in ventricle of model group was up-regulated by 46.45%,but there was no significant difference between spironolactone group and control group.The expression levels of PDGF-BB and TGF-β1 in the model group were significantly up-regulated by 70.14% and 118.47%,respectively.The spironolactone group was significantly lower than the model group,and there was no significant difference between the spironolactone group and the control group.The levels of c-Raf and ERK1/2 phosphorylation in the model group were significantly up-regulated by 106.25% and 74.00%,respectively,while the spironolactone group was not significantly different from the control group.The expression levels of c-myc and GATA4 mRNA in the model group were significantly up-regulated by 115.01% and 254.00%,respectively,while spironolactone treatment inhibited the up-regulation of c-myc a

关 键 词：左心室肥厚 螺内酯 压力超负荷 动物模型 c-Raf/ERK1/2信号通路 

分 类 号：R541.3[医药卫生—心血管疾病]