清肝益肾祛风方防治高血压心肌损伤的效应机制研究  

Study on mechanism of Qinggan Yishen Qufeng formula (QYQ) against hypertension-associated myocardial injury

作　　者：贾成林[1] 杜霄烨[1,2] 熊敏琪 崔金刚[1,2] 陈瑜[1,2] 张腾[1,2] JIA Chenglin;DU Xiaoye;XIONG Minqi;CUI Jingang;CHEN Yu;ZHANG Teng(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Clinical Research Institute of Integrated Chinese and Western Medicine,Shanghai Academy of Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海市中医药研究院中西医结合临床研究所,上海200437

出　　处：《上海中医药杂志》2019年第12期67-71,共5页Shanghai Journal of Traditional Chinese Medicine

基　　金：上海市卫计委进一步加快中医药事业发展三年行动计划项目[ZY(2018-2020)-CCCX-2004-07];上海市教委上海市高校东方学者跟踪计划项目[GZ2015011、沪教委人(2017)] 64号];上海市科委优秀学术带头人计划项目(19XD1403700);国家中医药管理局王文健全国名老中医药专家传承工作室项目(MLZJGZS-2017002)

摘　　要：目的探讨清肝益肾祛风方(QingganYishen Qufeng formula,QYQ)在高血压及高血压致心肌损伤双重病理条件下的干预效应及可能的作用机制。方法将自发性高血压大鼠随机分为模型组(SHR)、清肝益肾祛风方组(QYQ)、坎地沙坦组(Can),以8只同周龄雄性WKY大鼠作为正常对照组(WKY)。所有实验动物于6周龄起进行药物干预,共干预14周。各组大鼠均每隔2周通过尾压法测量收缩压及舒张压水平,以评价QYQ降压作用;20周龄时取心脏组织,石蜡包埋切片,HE染色计算心肌细胞横截面面积以评价QYQ对高血压心肌损伤的预防作用;同时进一步检测心脏组织中miR-125a-5p及其靶基因IL-6R、STAT3以及IL-6 mRNA的差异性表达。结果与模型组(SHR)比较,QYQ可显著降低SHR大鼠收缩压及舒张压水平(P<0.05),减少心肌细胞横截面面积(P<0.05),显著上调心脏组织中miR-125a-5p的表达,显著下调其直接靶基因IL-6R mRNA、STAT3 mRNA的表达,显著下调心脏组织中IL-6 mRNA的表达(P<0.05)。结论QYQ不仅具有显著的降压作用,且对高血压心肌损伤具有显著的预防作用;QYQ对miR-125a-5p/IL-6R/STAT3介导作用通路的调节作用可能是其防治高血压心肌损伤潜在的分子机制之一。Objective Objective To investigate the effects of Qinggan Yishen Qufeng formula( QYQ) on the dual pathological conditions of myocardial injury and high blood pressure as well as the possible mechanism. Methods Spontaneously hypertensive rats( SHRs) were randomly divided into QYQ-treated group( QYQ),Candesartan-treated group( Can) as well as the vehicle-treated groups( SHR). Eight male WKY rats of the same age were used as normal control group( WKY).All experimental animals were subject to drug intervention at 6 weeks of age for 14 weeks. The systolic and diastolic blood pressure levels were measured by the tail pressure method at every 2 weeks in each group to evaluate the effect of QYQ. At the age of 20 weeks,the cardiac tissue was taken and paraffin embedded section was performed. HE staining was used to calculate the cross-sectional area of the cardiac muscle cells to evaluate the preventive effect of QYQ on the hypertension-associated myocardial injury. The differential expression of miR-125 a-5 p and its target genes,such as IL-6 R,STAT3 and IL-6 mRNA in cardiac tissue was further tested. Results Compared with the model group,QYQ significantly decreased the systolic blood pressure( SBP) and diastolic blood pressure( DBP) of SHR rats,decreased the cross section area of cardio myocytes( P < 0. 05),upregulated the expression of miR-125 a-5 p in cardiac tissue,down-regulated the expression of direct target gene,such as IL-6 R,STAT3 mRNA, and down-regulated the expression of IL-6 mRNA in cardiac tissue( P<0.05). Conclusion QYQ not only has significant antihypertensive effect,but also has significant preventive effect on hypertension-associated myocardial injury. The regulatory effect of QYQ on miR-125 a-5 p/IL-6 R/STAT3 pathway may be one of the potential molecular mechanisms of QYQ in the prevention and treatment of hypertension-associated myocardial injury.

关 键 词：高血压 心肌损伤 大鼠 清肝益肾祛风方 分子机制 

分 类 号：R54[医药卫生—心血管疾病]