摘要
目的:探究黄蜀葵花有效成分黄蜀葵花总黄酮(TFA)在体内抑制糖尿病肾脏疾病(DKD)肾组织周细胞-肌成纤维细胞转分化(PMT)的作用和机制。方法:将30只大鼠随机分为假手术组、模型组、TFA组和伊马替尼(IMA)组。采用“高脂饲料喂养、单侧肾切除、链脲佐菌素(STZ)腹腔注射”3种措施联合建立改良型DKD大鼠模型。成模后,4组大鼠分别给予其双蒸水、TFA混悬液以及IMA混悬液灌胃,连续4周。在药物干预的第4周末,处死全部大鼠,收集尿液、血液和肾组织,采用肾组织病理染色、蛋白质分析和透射电子显微镜等技术进行检测和观察肾组织PMT相关指标。结果:与模型组比较,TFA组和IMA组UNAG与TFA组UACR水平显著降低(P<0.01);细胞外基质和肾间质胶原相对面积显著降低(P<0.01);TFA组和IMA组显著改善周细胞超微结构特征、周细胞和肌成纤维细胞标志分子蛋白表达强度和表达水平(P<0.01,P<0.05);TFA和IMA可以抑制肾组织血管内皮生长因子受体(PDGFR)、血小板源性生长因子受体(VEGFR)信号通路关键信号分子蛋白表达水平(P<0.05,P<0.01)。结论:TFA与IMA体内能改善DKD大鼠RIF,其机制可能是通过调控周细胞-内皮细胞相关PDGFR、VEGFR信号通路活性而抑制肾组织PMT。该研究为黄蜀葵花治疗DKD患者RIF提供了可靠的药理学证据。
Objective:To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA),an active ingredient from the flowers of Abelmoschus manihot treating diabetic kidney disease(DKD),in inhibiting pericytemyofibroblast transition(PMT).Methods:Thirty rats were randomly divided into the sham group,the model group,the TFA group and the Imatinib(IMA)group.The modified rat model with DKD was established by the combinative three methods including‘high fat feed,unilateral nephrectomy and streptozotocin(STZ)intraperitoneal injection’.After modeling successfully,the rats in four groups were given double distilled water,TFA suspension and IMA suspension respectively by intragastric administration every day for 4 weeks.At the end of the fourth week of the administration of drugs,all rats were sacrificed.The urine,blood and the kidneys were collected,respectively.And then the various indicators related to PMT in the kidney were examined and investigated respectively using a variety of techniques including renal histopathological staining,protein analysis and transmission electron microscopy.Results:Compared with the model group,the UNAG in the TFA group and IMA group and the UACR in the TFA group were significantly decreased(P<0.01);the extracellular matrix and the relative area of renal interstitial collagen were significantly decreased(P<0.01).TFA group and IMA group significantly ameliorated the ultrastructural characteristics of pericytes and the protein expression intensities and levels of markers in pericytes and myofibroblasts(MyoFs)(P<0.01,P<0.05);TFA group and IMA group significantly inhibited the protein expression levels of the key signaling molecules in platelet derived growth factor receptor(PDGFR)and vascular endothelial growth factor receptor(VEGFR)pathways in the kidney in varying degrees(P<0.05,P<0.01).Conclusion:TFA and IMA could improve RIF in the model rats with DKD,and its mechanism in vivo might be through regulating the activation of PDGFR and VEGFR signaling pathways related to p
作者
王美子
王玉
万毅刚
石岩
涂玥
史俪婧
黄露
武九龙
戴青青
龙燕
万子玥
WANG Mei-zi;WANG Yu;WAN Yi-gang;SHI Yan;TU Yue;SHI Li-jing;HUANG Lu;WU Jiu-long;DAI Qing-qing;LONG Yan;WAN Zi-yue(Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine,Nanjing 210008,China;Institute of Chinese Medicine,Nanjing University,Nanjing 210008,China;Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China;Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Acupuncture and Moxibustion and Massage College·Health Preservation and Rehabilitation College,Nanjing University of Chinese Medicine,Nanjing 210023,China;Graduate School of Social Sciences,Faculty of Social Sciences,Hitotsubashi University,Tokyo 186-8601,Japan)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2022年第5期2856-2861,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金面上项目(No.81573903,No.82174472)
国家自然科学基金青年科学基金项目(No.81603675)
江苏省自然科学基金面上项目(No.BK20211298)
江苏省自然科学基金青年科学基金项目(No.BK20161046)
中央高校基本科研业务费专项(No.021414380518)
江苏省研究生科研与实践创新计划项目(No.KYCX21_1699)
南京市名中医专家工作室建设项目。
