清肝益肾袪风复方干预高血压肠道屏障功能失调的效应机制研究  

Effects and Mechanisms of Qinggan Yishen Qufeng Formula in the Treatment Against Gut Barrier Dysfunction in Hypertension

作　　者：熊敏琪[1,2] 唐晓婷 崔金刚[1,2] 丁李立强 唐新淼 王培伟[1,2] 陈瑜 张腾[1,2] Xiong Minqi;Tang Xiaoting;Cui Jingang;Dingli Liqiang;Tang Xinmiao;Wang Peiwei;Chen Yu;Zhang Teng(Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Clinical Institute of Integrative Chinese-Western Medicine,Shanghai Academy of Traditional 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：《世界科学技术-中医药现代化》2019年第9期1939-1947,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：上海市教委高校特聘教授（东方学者）跟踪计划（GZ2015011）：中西医结合临床，负责人：张腾;上海市卫计委关于进一步加快中医药事业发展三年行动计划（2018年-2020年）（ZY（2018-2020）-CCCX-2004-07）：中医药防治高血压及靶器官损伤的优势效应机制研究，负责人：张腾

摘　　要：目的探索清肝益肾袪风复方(Qinggan Yishen Qufeng formula,QYQ)对大鼠高血压肠道屏障功能失调的干预效应。方法以4周龄自发性高血压大鼠(Spontaneously Hypertensive Rats,SHR)为研究对象,将其随机分为模型组、清肝益肾袪风复方组(QYQ)、坎地沙坦酯片组(Can),以同周龄WKY雄性大鼠为正常对照组,持续干预至8周龄,12周龄和20周龄。通过FITC-dextran实验检测肠道渗透性;用HE染色和Masson’s trichrome染色观察回肠及近端结肠病理形态学改变和肠道粘膜下纤维化;采用Real Time-PCR分析紧密连接蛋白Cgn、Ocln、Tjp1 mRNA表达水平。结果①肠道渗透性分析结果表明:20周龄时,与WKY组相比,SHR模型组血清FITC-dextran浓度显著升高(P<0.05),与SHR模型组相比,QYQ治疗组血清FITCdextran浓度降低(P<0.05),提示QYQ显著改善肠道渗透性,而Can组与SHR模型组相比,血清FITCdextran浓度无显著性差异。②组织病理学分析结果表明:20周龄时,与WKY组相比,SHR模型组回肠组织病理损伤评分显著升高(P<0.05);与SHR模型组相比,QYQ治疗组回肠组织病理损伤评分显著降低(P<0.05)。12周龄及20周龄时,与WKY组相比,SHR模型组结肠组织病理损伤评分升高,差异显著(P<0.05);20周龄时,QYQ治疗组结肠组织病理损伤评分显著低于SHR模型组(P<0.05)。此外,回肠和结肠组织Massons trichrome染色分析结果表明:8周龄、12周龄及20周龄时,与WKY组相比较,SHR模型组纤维化相对面积显著升高,有统计学差异(P<0.05)。20周龄时,与SHR模型组相比较,QYQ治疗组回肠及结肠纤维化相对面积显著降低,有统计学差异(P<0.05)。③紧密连接蛋白表达分析结果表明:20周龄时,与WKY组相比,SHR模型组回肠组织紧密连接蛋白Cgn、Ocln、Tjp1 mRNA表达水平显著降低(P<0.05);与SHR模型组相比,QYQ治疗组Cgn、Ocln、Tjp1 mRNA表达水平显著升高(P<0.05),且Ocln mRNA表达水平高于Can组(P<0.05)。20周龄时,与WKY组相比,SHR模型组结Objective To investigate the effects and mechanisms of Qinggan Yishen Qufeng Formula(QYQ)in the treatment against gut barrier dysfunction in hypertension.Methods Four-week old spontaneously hypertensive rats were randomly divided to a vehicle-treated group(SHR),a Qinggan Yishen Qufeng formula-treated group(QYQ)and a candesartan-treated group,vehicle-treated WKY included as normal controls,with continuous intervention up to 8 weeks of age,12 weeks of age and 20 weeks of age.The gut permeability was detected by FITC-dextran assay.HE staining and Masson′s trichrome staining of ileum and proximal colon were performed to characterize histopathological examination.The expression of genes encoding tight junction proteins such as Cgn,Ocln and Tjp1 was examined using real time-PCR.Results①The gut permeability analysis indicated that the serum FITC-dextran concentration of SHRs was significantly higher that WKY rats at the age of 20 weeks(P<0.05);Compared with SHRs,the serum FITC-dextran concentration of QYQ-treated rats was significantly lower(P<0.05),indicating the beneficial change in gut permeability of QYQ.However,there was no significant difference concerning the serum FITC-dextran concentration between Can-treated rats and SHRs(P>0.05).②Histopathological analysis indicated that compared with WKY group,the ileum histopathological injury score was significantly higher in SHR group at the age of 20 weeks(P<0.05);Compared with the SHR group,the ileum histopathological injury score of QYQ-treated group was significantly lower(P<0.05).At the age of 12 weeks and 20 weeks,compared with WKY group,the colon histopathological injury score was significantly higher in SHR group(P<0.05);At the age of 20 weeks,the colon histopathological injury score of QYQ-treated group was significantly lower than SHR group(P<0.05).Moreover,the HE and Masson′s trichrome staining results indicated that at the age of 8 weeks,12 weeks and 20 weeks,compared with WKY group,the fibrotic area of SHR group was significantly higher(P<0.05).At the

关 键 词：高血压 清肝益肾袪风复方 肠道屏障功能 

分 类 号：R289.5[医药卫生—方剂学]