黄芪-丹参改善肾脏纤维化的研究进展

Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma Mitigate Renal Fibrosis: A Review

肾脏纤维化是慢性肾脏病进展为终末期肾脏病的最终病理归途,与炎症反应、氧化应激、上皮-间充质转化和细胞外基质沉积密切相关。中医属“水肿”“癃闭”“关格”“虚劳”等范畴,病机关键为气虚血瘀,补气活血为主要治则。黄芪-丹参药对主要含黄芪皂苷、黄芪多糖、毛蕊异黄酮、丹酚酸、丹参酮等成分,具有补气活血之功效。多项研究表明,黄芪-丹参药对及其有效组分可通过调节与肾脏纤维化相关的多个信号转导通路,改善肾脏纤维化、延缓其进展。该文基于肾脏纤维化本虚标实、气虚血瘀的病因病机,从保护肾小球滤过屏障、抑制肾小管上皮-间充质转化及系膜细胞增殖、改善肾脏血流动力学、保护肾功能方面探讨共奏益气活血之效的黄芪-丹参药对及其有效组分在改善肾脏纤维化中的研究进展,并进一步总结、分析、阐述其作用机制,得出黄芪丹参及其有效组分主要通过调控核转录因子E2相关因子2(Nrf2)/PTEN诱导激酶1(Pink1)、Nrf2/抗氧化反应元件(ARE)、肿瘤坏死因子-α(TNF-α)/核转录因子-κB(NF-κB)、miR-21/Smad7/转化生长因子-β(TGF-β)、Wnt/β-连环蛋白(β-catenin)、长链非编码RNA-牛磺酸上调基因1(lncRNA-TUG1)/肿瘤坏死因子受体相关因子5(TRAF5)、Ras相关的C3肉毒素底物1(Rac1)/细胞分裂周期蛋白42(CDC42)、Ras同源基因家族蛋白(Rho)/Rho相关卷曲螺旋蛋白激酶(ROCK)、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)、Janus酪氨酸蛋白激酶(JAK)/信号转导及转录激活因子(STAT)、过氧化物酶体增殖物激活受体α(PPARα)/过氧化物酶体增殖物激活受体γ辅激活因子-1α(PGC-1α)、p38丝裂原活化蛋白激酶(p38 MAPK)等信号通路,改善线粒体功能、内质网应激、脂肪酸代谢、自噬紊乱,抑制免疫炎症及氧化应激,进而改善肾脏纤维化,以期为其在肾脏纤维化中的研究提供借鉴,并进一步发挥其在临床中的应用价值,为临床治疗提供科学的指导和依据。

Renal fibrosis,the final pathological outcome of end-stage chronic kidney diseases,is associated with inflammation,oxidative stress,epithelial-mesenchymal transdifferentiation(EMT),and extracellular matrix deposition.It belongs to the categories of edema,ischuria,anuria and vomiting,and consumptive disease in traditional Chinese medicine(TCM),with the key pathogenesis of Qi deficiency and blood stasis and the primary treatment principle of replenishing Qi and activating blood.Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma mainly contains astragalosides,polysaccharides,calycosin,salvianolic acid,and tanshinone,with the effect of tonifying Qi and activating blood.Studies have shown that this herb pair and its active components can delay the progress of renal fibrosis by regulating multiple signaling pathways.With consideration to the pathogenesis of Qi deficiency and blood stasis,this article reviews the research progress in the mitigation of renal fibrosis by Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma from the aspects of protecting glomerular filtration barrier,inhibiting EMT and mesangial cell proliferation,improving renal hemodynamics,and protecting renal function.Furthermore,the mechanisms were summarized.Specifically,Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and its effective components can improve mitochondrial function and fatty acid metabolism,alleviate endoplasmic reticulum stress and autophagy disorders,and inhibit immune inflammation and oxidative stress by regulating nuclear factor E2-related factor 2(Nrf2)/PTEN-induced kinase 1(Pink1),Nrf2/antioxidant response element(ARE),tumor necrosis factor-α(TNF-α)/nuclear transcription factor-κB(NF-κB),miR-21/Smad7/transforming growth factor beta(TGF-β),Wnt/β-catenin,long non-coding RNA-taurine up-regulated gene 1(lncRNA-TUG1)/tumor necrosis factor receptor-associated factor 5(TRAF5),Ras-related C3 botulinum toxin substrate 1(Rac1)/cell division cycle protein 42(CDC42),Ras homolog(Rho)/Rho-associated coiled-coil containing protein kinase(ROCK),phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt),Janus kinase(JAK)/signal transducer and activator of transcription(STAT),peroxisome proliferator-activated receptorα(PPARα)/peroxisome proliferator-activated receptorγcoactivator l alpha(PGC-1α),and p38 mitogen-activated protein kinase(p38 MAPK).This review aims to provide references for the relevant research,give play to the role of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma,and provide guidance for the clinical treatment of renal fibrosis.