Mesh : Animals Humans Rats Creatinine Extracellular Matrix Proteins Fibrinogen Fibronectins Kidney Failure, Chronic / drug therapy Renal Insufficiency, Chronic / drug therapy Serpins Transforming Growth Factor beta Transforming Growth Factor beta1 Vitronectin

来  源:   DOI:10.1097/MD.0000000000037473   PDF(Pubmed)

Abstract:
Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-β1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-β1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-β, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-β, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).
摘要:
慢性肾功能衰竭(CRF)导致肾小球滤过率降低和肾实质损害。复生宫汤(FSGD)可改善CRF大鼠的肾功能。本研究旨在分析单独使用西药或与FSGD联合治疗的CRF患者的差异表达蛋白。将重庆医科大学附属永川中医医院收治的60例CRF患者随机分为对照组(单纯西药治疗)和观察组(每天3次,共8周)。临床疗效及血清Bun,血清肌酐,胱抑素C,观察治疗前后转化生长因子β1(TGF-β1)的变化。我们使用同位素相对标记绝对定量标记和液相色谱-质谱来鉴定差异表达的蛋白质,并进行了生物信息学基因本体论和京都基因和基因组百科全书分析。观察组患者临床改善较大,血清Bun水平较低,血清肌酐,Cyc-c,而TGF-β1高于对照组。我们在观察组中鉴定了32种差异上调和52种差异下调的蛋白质。这些蛋白质参与血液凝固系统,蛋白丝氨酸/苏氨酸激酶活性,和TGF-β,与CRF的发病机制密切相关。蛋白质-蛋白质-相互作用网络分析表明候选蛋白纤连蛋白1,纤维蛋白原α链,玻连蛋白,和Serpin系列C成员1在关键节点中。本研究提供了实验依据,提示FSGD联合西药可显著改善CRF患者的肾功能及肾纤维化,这可能是通过纤维连接蛋白1,纤维蛋白原α链的调节,玻连蛋白,Serpin家族C成员1,TGF-β,和补体凝血途径(见图形摘要S1,补充数字内容,http://链接。lww.com/MD/L947).
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