基于“湿、热、瘀”论治胆汁淤积性肝病的研究

Study on Treatment of Cholestatic Liver Disease Based on"Dampness,Heat and Blood Stasis"

胆汁淤积性肝病(cholestasis liver disease,CSLD)是因胆汁生成、分泌及排泄障碍导致肝内外胆汁淤积的临床常见疾病,中医药基于“湿、热、瘀”的病因病机干预CSLD具有特色及优势。故本文回顾古今医家关于CSLD“湿、热、瘀”病因病机特点的论述,结合CSLD现代医学特征与分子生物学研究,发现从“湿、热、瘀”论治CSLD可调控胆汁酸代谢的关键靶点,通过激活法尼酯衍生物X受体(farnesoid X receptor,FXR),下调牛磺胆酸钠共转运多肽(sodium taurocholate co-transport polypeptide,NTCP)、诱导胆盐输出泵(bile salt output pump,BSEP),并激活G蛋白偶联胆汁酸受体5(G-protein coupled-receptor kinase,TGR5),抑制NF-κB信号通路,调节细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)及AMP依赖性蛋白激酶(AMP-activated protein kinase,AMPK)的途径,以恢复机体正常的胆汁酸及胆汁代谢,发挥利胆、抗炎、调节多项相关肝功能指标的药理学作用,可为中医应用清湿祛瘀法治疗CSLD提供理论支持,为中医防治CSLD提供思路。

Cholestatic liver disease(CSLD)is a common clinical disease caused by cholestasis inside or outside the liver due to the obstruction of bile production,secretion and excretion.Traditional Chinese medicine(TCM)has its characteristics and advantages in the intervention of etiology and pathogenesis to CSLD based on"dampness,heat and blood stasis".This paper reviewed the ancient and modern physicians about CSLD"dampness,heat,blood stasis"pathogenesis characteristics,combined with the feature of the CSLD modern medicine and molecular biology research,found that from the"dampness,heat,blood stasis"differentiation CSLD to treat can adjust and control the key targets of bile acid metabolism.It can down-regulate of sodium taurocholate cotransport polypeptide(NTCP)and induce bile salt export pump(BESP)by activating Farnesoid derivative X receptor(FXR);inhibit NF-κB signaling pathway and regulate extracellular signal-regulated kinase(ERK)and AMP-dependent protein kinase(AMPK)by activating G protein coupled bile acid receptor 5(TGR5).So as to restore normal bile acid and bile metabolism in the body,and play a pharmacological role of choleretic effect,anti-inflammation and several related liver function indicators regulation,which can provide theoretical support for TCM treatment of CSLD with the method of clearing heat,removing dampness and blood stasis,and provide ideas for TCM prevention and treatment of CSLD.