从“Wnt/β-catenin-伏毒”论肾纤维化病因病机
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摘要
肾纤维化是各种不同病因的肾性疾病发展致终末期肾衰竭的共同病理表现。大量实验表明Wnt/β-catenin信号通路参与肾纤维化的发生发展,通过抑制Wnt/β-catenin信号通路活化可延缓肾纤维化进程。Wnt/β-catenin信号通路和相关蛋白突变及异常介导肾纤维化发生过程与伏毒病理过程有着相似之处,而它介导炎症状态也与中医内生伏毒"湿(浊、痰)、瘀、毒"类同,肾纤维现代病理观也同中医伏毒所致的微型癥积相似。故从Wnt/β-catenin信号通路与肾纤维化的关系、肾纤维化病因病机与伏毒关系、肾纤维化中西医病理观、中医药延缓肾纤维化进展机制方面来探讨肾纤维化的病因病机。
Renal fibrosis is a common pathological manifestation of end-stage renal failure resulting from the development of various renal diseases. A large number of experiments have shown that Wnt/β-catenin signaling pathway is involved in the occurrence and development of renal fibrosis, and it can delay the progression of renal fibrosis by inhibiting the activation of Wnt/β-catenin signaling pathway. Mutations and abnormalities in the Wnt/β-catenin signaling pathway and related proteins are involved in the pathogenesis of renal fibrosis and have similarities with the pathogenesis of vaccination, and it mediates the inflammatory state and endogenous toxins in Chinese medicine. Dampness(phlegm, turbid),stasis and poison are similar. The modern pathological concept of kidney fiber is also similar to that caused by the poisoning in traditional Chinese medicine. Therefore, we discussed renal fibrosis by examining the relationship between Wnt/β-catenin signaling pathway and renal fibrosis, the pathogenesis of renal fibrosis and the relationship between saporosis, kidney fibrosis, traditional Chinese and Western pathology and the mechanism of Chinese medicine delaying etiology and pathogenesis of renal fibrosis progression.
Renal fibrosis is a common pathological manifestation of end-stage renal failure resulting from the development of various renal diseases. A large number of experiments have shown that Wnt/β-catenin signaling pathway is involved in the occurrence and development of renal fibrosis, and it can delay the progression of renal fibrosis by inhibiting the activation of Wnt/β-catenin signaling pathway. Mutations and abnormalities in the Wnt/β-catenin signaling pathway and related proteins are involved in the pathogenesis of renal fibrosis and have similarities with the pathogenesis of vaccination, and it mediates the inflammatory state and endogenous toxins in Chinese medicine. Dampness(phlegm, turbid),stasis and poison are similar. The modern pathological concept of kidney fiber is also similar to that caused by the poisoning in traditional Chinese medicine. Therefore, we discussed renal fibrosis by examining the relationship between Wnt/β-catenin signaling pathway and renal fibrosis, the pathogenesis of renal fibrosis and the relationship between saporosis, kidney fibrosis, traditional Chinese and Western pathology and the mechanism of Chinese medicine delaying etiology and pathogenesis of renal fibrosis progression.
引文
[1] He X. Cilia put a brake on Wnt signaling[J]. Nat Cell Biol, 2008, 10(1):11-13.
[2] Xiao L, Wang M, Yang S, et al. A glimpse of the pathogeneticmechanisms of Wnt/β- catenin signaling in diabetic nephropathy[J]. Biomed Res Int, 2013, 2013: 987064.
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[5] Bienz M.Beta-Catenin: a prvet between cell adhesion and wnt signaling[J].Curr Biol,2005,15(2): 1764-1767.
[6] Surendran K,Simon TC,Liapis H,et al.Matrilysin(MMP-7) expression in renal tubular damage:association with Wnt4[J].Kidney Int,2010,71(6): 3212-3222.
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[11] 吴素珍,李加林,吴冰,等.转化生长因子-β在糖尿病肾病肾小球硬化中的作用[J].赣南医学院学报,2017,37(2):312-337.
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[19] 向玉琼,李素文,肖争,等.去甲斑鳌素对梗阻性肾病Wnt/β-catenin表达的影响[J].肾脏病与透析肾移植杂志,2015,24(4):348-353.
[20] 付旭,李均,阳小敏 ,等.黄芪丹参颗粒药对干预肾纤维化Wnt/β-catenin信号通路的实验研究[J].世界科学技术—中医药现代化,2014,16(1):103-107.
[21] 任克军,王东,王亿平,等. 清肾颗粒对单侧输尿管梗阻致肾间质纤维化大鼠肾组织Wnt/β-catenin信号通路的干预作用[J]. 安徽中医药大学学报,2017,36(2): 60-63.
[22] 罗婷,程锦国,姜程曦,等. 清化固肾排毒颗粒对肾纤维化大鼠Wnt通路Wnt1和β-catenin表达的影响[J]. 中草药,2016,47(6):955-962.
[23] 吴小燕,李丽艳,项协隆,等.“清化固肾排毒颗粒”对单侧输尿管梗阻大鼠肾组织Wnt4 和TGF-β1表达的影响[J].江苏中医药,2016,48(8):75-77.
[2] Xiao L, Wang M, Yang S, et al. A glimpse of the pathogeneticmechanisms of Wnt/β- catenin signaling in diabetic nephropathy[J]. Biomed Res Int, 2013, 2013: 987064.
[3] YookⅡ,Li XY,Ota I,et al.Wnt—dependent regulation of the E—cadherin repressor snail[J].J Biol Chem,2008,280(12):11740-11748.
[4] He X. Cilia put a brake on Wnt signaling[J]. Nat Cell Biol, 2008, 10(1):11-13.
[5] Bienz M.Beta-Catenin: a prvet between cell adhesion and wnt signaling[J].Curr Biol,2005,15(2): 1764-1767.
[6] Surendran K,Simon TC,Liapis H,et al.Matrilysin(MMP-7) expression in renal tubular damage:association with Wnt4[J].Kidney Int,2010,71(6): 3212-3222.
[7] Behrens J. The role of the wnt signalling pathway in colorectal tumorigenesls[J]. Biochem Soc Trans, 2008, 36(4):1672-1675.
[8] 郑颖,张璟,卓文磊,等.TGFβ-1对人肾小管上皮细胞表达糖原合成酶激酶-3β的影响[J].重庆医学,2007(5): 414-416.
[9] 周仲瑛.“伏毒”新识[J].世界中医药,2007,2(2):73.
[10] 胡蓉,王明清,刘阳阳,等.肾衰营养胶囊对5/6肾切除慢性肾衰大鼠微炎症状态血管损伤的抗炎作用[J].广东医学,2016,37(22):3345-3348.
[11] 吴素珍,李加林,吴冰,等.转化生长因子-β在糖尿病肾病肾小球硬化中的作用[J].赣南医学院学报,2017,37(2):312-337.
[12] 曹式丽,王宁.肾络病证的核心特征与临床药物筛选原则[J].天津中医药,2007(6):486-488.
[13] 邓文超,方敬爱. 黄芪对糖尿病肾病大鼠肾间质Wnt/β-catenin及TGF-β1信号通路表达的影响[J].中国中西医结合肾病杂志,2012(7):571-574.
[14] 陈烨,朱春玲,严瑞,等.山茱萸对肾间质纤维化的保护作用及机制研究[J].天然产物研究与开发,2015,27:1957-1961.
[15] 张涛,朱小军,陈慧.大黄酸对高糖诱导人肾小球系膜细胞wnt/β-catenin蛋白及TGF-β1表达的影响[J]. 环球中医药,2015,8(s2):155-156.
[16] 石格,吴薇,万毅刚,等.低剂量雷公藤甲素抑制 Wnt3α/β-catenin 信号通路活性改善高剂量D-葡萄糖诱导的足细胞转分化[J].中国中药杂志,2018,43(1):139-146.
[17] 王曼,王新宇,陈叶香,等.丹酚酸B干预肾间质纤维化Wnt/β- catenin信号通路的研究[J].中药新药与临床药理,2016,27(5):602-607.
[18] 白璐,霍贝贝,郭倩,等.Wnt/β-catenin 通路在糖尿病肾病大鼠的表达及化瘀通络中药的干预作[J].中草药,2017,48(5):946-950.
[19] 向玉琼,李素文,肖争,等.去甲斑鳌素对梗阻性肾病Wnt/β-catenin表达的影响[J].肾脏病与透析肾移植杂志,2015,24(4):348-353.
[20] 付旭,李均,阳小敏 ,等.黄芪丹参颗粒药对干预肾纤维化Wnt/β-catenin信号通路的实验研究[J].世界科学技术—中医药现代化,2014,16(1):103-107.
[21] 任克军,王东,王亿平,等. 清肾颗粒对单侧输尿管梗阻致肾间质纤维化大鼠肾组织Wnt/β-catenin信号通路的干预作用[J]. 安徽中医药大学学报,2017,36(2): 60-63.
[22] 罗婷,程锦国,姜程曦,等. 清化固肾排毒颗粒对肾纤维化大鼠Wnt通路Wnt1和β-catenin表达的影响[J]. 中草药,2016,47(6):955-962.
[23] 吴小燕,李丽艳,项协隆,等.“清化固肾排毒颗粒”对单侧输尿管梗阻大鼠肾组织Wnt4 和TGF-β1表达的影响[J].江苏中医药,2016,48(8):75-77.