清达颗粒调控TGF-β1/Smad2/3通路减轻高血压肾动脉血管纤维化  

Qingda Granules Alleviates Renal Artery Vascular Fibrosis in Hypertension via Regulating TGF-β1/Smad2/3 Pathway

作　　者：陈红 郭智 吴美珠 林国晟 刘丽雅 彭军 沈阿灵 CHEN Hong;GUO Zhi;WU Mei-zhu;LIN Guo-sheng;LIU Li-ya;PENG Jun;SHEN A-ling(Academy of Integrative Medicine,College of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,350122;Fujian Key Laboratory of Integrative Medicine on Geriatrics,Fuzhou,350122;Geriatric Rehabilitation Department,Fujian University of Traditional Chinese Medicine Affiliated Rehabilitation Hospital,Fuzhou,350003)

机构地区：[1]福建中医药大学中西医结合研究院,中西医结合学院,福州350122 [2]福建省中西医结合老年性疾病重点实验室,福州350122 [3]福建中医药大学附属康复医院老年康复科,福州350003

出　　处：《中国中西医结合杂志》2025年第1期70-76,共7页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：福建中医药大学中医康复学科开放课题(No.XKF2023012);福建省卫生健康中青年领军人才研修培养项目资助(No.闽卫人函[2023]2841);2022年度校青年科研拔尖人才项目(No.XQB202201);福建省第二批“雏鹰计划”青年拔尖人才(No.2021-QNRC2-B19)。

摘　　要：目的探讨清达颗粒(QDG)对高血压病所致肾动脉纤维化的影响。方法选择6只Wistar-Kyoto大鼠(WKY)作为对照组。选择自发性高血压大鼠(SHR)30只,按照随机数字表法分为模型组、QDG低剂量组、中剂量组、高剂量组及阳性药组,每组6只。QDG低、中、高剂量组分别按450、900、1800 mg/(kg·d)给予QDG灌胃,阳性药组按7.2 mg/(kg·d)给予缬沙坦灌胃,对照组和模型组大鼠均给予等体积的双蒸水灌胃,每日1次,连续10周。采用HE染色法观察肾动脉病理变化,通过RNA测序分析差异表达转录本,利用GO和KEGG分析富集潜在相关通路。通过血管紧张素Ⅱ(AngⅡ)刺激构建肾动脉血管平滑肌细胞的体外模型,验证不同剂量QDG对纤维化及潜在富集通路活化的影响。结果不同剂量的QDG均可降低SHR肾动脉中膜厚度(P<0.05)。QDG干预后,共有1423个差异表达的转录本发生变化。GO分析发现细胞和生物过程等被显著富集;KEGG分析发现丝裂原活化蛋白激酶(MAPK)和转化生长因子β(TGF-β)等通路被显著富集。QDG干预能抑制AngⅡ刺激后肾动脉平滑肌细胞中Ⅰ型胶原蛋白(CollagenⅠ)、Ⅲ型胶原蛋白(CollagenⅢ)、基质金属蛋白酶9(MMP9)、p-Smad2、p-Smad3、TGF-β1蛋白表达,提高基质金属蛋白酶组织抑制剂(TIMP)-1和TIMP2蛋白表达(P<0.05)。结论QDG抑制TGFβ-1/Smad2/3通路活化减轻高血压所致肾动脉血管纤维化。Objective To investigate the effect of Qingda Granules(QDG)on renal artery fibrosis induced by hypertension.Methods Six WKY rats were selected to serve as the control group.Totally 30 spontaneously hypertensive rats(SHRs)were randomly divided into the model group,low-dose QDG group,medium-dose QDG group,high-dose QDG group,and the positive drug group,with six rats in each group.The QDG low,medium,and high dose groups were administered with QDG intragastrically at doses of 450,900,and 1800 mg·kg-1·d-1,respectively,while the positive drug group was given valsartan intragastrically at a dose of 7.2 mg·kg-1·d-1.Both the control and model groups were intragastrically administered with an equivalent volume of double-distilled water,once daily for 10 consecutive weeks.HE staining was used to detect the pathological changes of renal artery tissue.RNA sequencing was used to analyze differentially expressed transcripts,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the potential pathways.AngiotensinⅡ(AngⅡ)stimulation was used to establish a model of rat renal artery vascular smooth muscle cells to verify the effects of different doses of QDG on fibrosis and activation of potential enrichment pathways.Results QDG significantly reduced the thickness of renal artery media in SHR rats(P<0.05).RNA sequencing analysis indicated that 1423 differential transcripts changed after QDG intervention.GO analysis showed that cellular processes and biological processes were significantly enriched.KEGG analysis found that mitogen-activated protein kinase(MAPK),transforming growth factorβ(TGF-β)and other pathways were significantly enriched.QDG significantly inhibited the protein expressions of CollagenⅠ,CollagenⅢ,matrix metalloproteinase 9(MMP-9),p-Smad2,p-Smad3,and TGF-β1 in rat renal artery vascular smooth muscle cells stimulated by AngⅡ,and increased the protein expressions of tissue inhibitor of metalloproteinase(TIMP)1 and TIMP2(P<0.05).Conclusions QDG inhibits the activatio

关 键 词：高血压病 清达颗粒 肾动脉 纤维化 TGF-β1/Smad2/3信号通路 中药复方 中西医结合 

分 类 号：R285.5[医药卫生—中药学]