1.上海中医药大学附属曙光医院肾病科(上海 201203)
2.上海中医药大学中医肾病研究所(上海 201203)
3.肝肾疾病病证教育部重点实验室(上海 201203)
4.上海市中医临床重点实验室(上海 201203)
王婉婷,女,硕士研究生,主要从事中医药防治肾脏病的基础与临床研究工作
邵命海,主任医师,硕士研究生导师; E-mail: meck.wx@163.com
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王婉婷,许颖,邵命海.中药单体靶向PI3K/Akt/mTOR信号通路防治糖尿病肾病的研究进展[J].上海中医药杂志,2023,57(10):83-88.
WANG Wanting,XU Ying,SHAO Minghai.Research progress in monomers of traditional Chinese herbal medicine targeting PI3K/Akt/mTOR signaling pathway to prevent and treat diabetic nephropathy[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(10):83-88.
王婉婷,许颖,邵命海.中药单体靶向PI3K/Akt/mTOR信号通路防治糖尿病肾病的研究进展[J].上海中医药杂志,2023,57(10):83-88. DOI: 10.16305/j.1007-1334.2023.2301019.
WANG Wanting,XU Ying,SHAO Minghai.Research progress in monomers of traditional Chinese herbal medicine targeting PI3K/Akt/mTOR signaling pathway to prevent and treat diabetic nephropathy[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(10):83-88. DOI: 10.16305/j.1007-1334.2023.2301019.
综述中药单体靶向磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路防治糖尿病肾病(DN)的研究进展。研究表明,PI3K/Akt/mTOR信号通路可以抑制炎症反应、氧化应激、细胞凋亡和自噬,在DN发生发展中起着重要作用;中药单体(黄芩苷、石斛碱、姜黄素、三七皂苷R1、桔梗皂苷D、蛇床子素)可通过靶向调控该信号通路有效防治DN。
This article reviewed the research progress in monomers of traditional Chinese herbal medicine targeting PI3K/Akt/mTOR signaling pathway to prevent and treat diabetic nephropathy (DN). Studies have shown that PI3K/Akt/mTOR signaling pathway can inhibit inflammatory reaction, oxidative stress, apoptosis and autophagy, and plays an important role in the development and progression of DN. Monomers of traditional Chinese herbal medicine (baicalin, dendrobine, curcumin, notoginsenoside R1, platycodin D and osthole) can effectively prevent and treat DN by regulating PI3K/Akt/mTOR signaling pathway.
糖尿病肾病中药作用机制研究进展
diabetic nephropathytraditional Chinese herbal medicinemechanism of actionresearch progress
MARTINEZ-CASTELAO A, NAVARRO-GONZALEZ J F, GORRIZ J L, et al. The concept and the epidemiology of diabetic nephropathy have changed in recent years[J]. J Clin Med, 2015, 4(6): 1207-1216.
DONG Y, ZHAO Q, WANG Y. Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy[J]. Sci Rep, 2021, 11(1): 19496.
YANG Y Q, TAN H B, ZHANG X Y, et al. The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against renal injury and inflammation in mice with diabetic kidney disease[J]. J Ethnopharmacol, 2022, 292: 115165.
黄芸,张治楠,黄泳,等. PI3K-AKT信号通路与抑郁症的关系及中医干预作用研究进展[J]. 上海中医药杂志,2020, 54(2): 108-112.
GUO H, GERMAN P, BAI S, et al. The PI3K/AKT pathway and renal cell carcinoma[J]. J Genet Genomics, 2015, 42(7): 343-353.
MANNING B D, TOKER A. AKT/PKB signaling: navigating the network[J]. Cell, 2017, 169(3): 381-405.
DIBBLE C C, CANTLEY L C. Regulation of mTORC1 by PI3K signaling[J]. Trends Cell Biol, 2015, 25(9): 545-555.
GUI Y, DAI C. mTOR signaling in kidney diseases[J]. Kidney360, 2020, 1(11): 1319-1327.
ELSHERBINY N M, AL-GAYYAR M M. The role of IL-18 in type 1 diabetic nephropathy: the problem and future treatment[J]. Cytokine, 2016, 81: 15-22.
LIN Y C, CHANG Y H, YANG S Y, et al. Update of pathophysiology and management of diabetic kidney disease[J]. J Formos Med Assoc, 2018, 117(8): 662-675.
WARREN A M, KNUDSEN S T, COOPER M E. Diabetic nephropathy: an insight into molecular mechanisms and emerging therapies[J]. Expert Opin Ther Targets, 2019, 23(7): 579-591.
苏华华,王艳华. PI3K/AKT/mTOR信号通路在骨肉瘤中的作用[J]. 生命的化学, 2021, 41(5): 964-971.
HONG J N, LI W W, WANG L L, et al. Jiangtang decoction ameliorate diabetic nephropathy through the regulation of PI3K/Akt-mediated NF-κB pathways in KK-Ay mice[J]. Chin Med, 2017, 12: 13.
COUGHLAN M T, SHARMA K. Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease[J]. Kidney Int, 2016, 90(2): 272-279.
GUCLUA, YONGUCN, DODURGA Y, et al. The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats[J]. Ren Fail, 2015, 37(2): 192-197.
SHARMA D, BHATTACHARYA P, KALIA K, et al. Diabetic nephropathy: new insights into established therapeutic paradigms and novel molecular targets[J]. Diabetes Res Clin Pract, 2017, 128: 91-108.
KATO M, NATARAJAN R. Diabetic nephropathy--emerging epigenetic mechanisms[J]. Nat Rev Nephrol, 2014, 10(9): 517-530.
WIGHT T N, POTTER-PERIGO S. The extracellular matrix: an active or passive player in fibrosis?[J]. Am J Physiol Gastrointest Liver Physiol, 2011, 301(6): G950-G955.
LU Q, WANG W W, ZHANG M Z, et al. ROS induces epithelial-mesenchymal transition via the TGF-β1/PI3K/Akt/mTOR pathway in diabetic nephropathy[J]. Exp Ther Med, 2019, 17(1): 835-846.
LIAO J, LIU B, CHEN K, et al. Galangin attenuates oxidative stress-mediated apoptosis in high glucose-induced renal tubular epithelial cells through modulating renin-angiotensin system and PI3K/AKT/mTOR pathway[J]. Toxicol Res (Camb), 2021, 10(3): 551-560.
KIM K C, LEE I K, KANG K A, et al. 7,8-Dihydroxyflavone suppresses oxidative stress-induced base modification in DNA via induction of the repair enzyme 8-oxoguanine DNA glycosylase-1[J]. Biomed Res Int, 2013, 2013: 863720.
MAEZAWA Y, TAKEMOTO M, YOKOTE K. Cell biology of diabetic nephropathy: roles of endothelial cells, tubulointerstitial cells and podocytes[J]. J Diabetes Investig, 2015, 6(1): 3-15.
GARDAI S J, HILDEMAN D A, FRANKEL S K, et al. Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils[J]. J Biol Chem, 2004, 279(20): 21085-21095.
QI X J, WILDEY G M, HOWE P H. Evidence that Ser87 of BimEL is phosphorylated by Akt and regulates BimEL apoptotic function[J]. J Biol Chem, 2006, 281(2): 813-823.
PARCELLIER A, TINTIGNAC L A, ZHURAVLEVA E, et al. PKB and the mitochondria: AKTing on apoptosis[J]. Cell Signal, 2008, 20(1): 21-30.
SU H C, MA C T, YU B C, et al. Glycogen synthase kinase-3β regulates anti-inflammatory property of fluoxetine[J]. Int Immunopharmacol, 2012, 14(2): 150-156.
BENDER A, OPEL D, NAUMANN I, et al. PI3K inhibitors prime neuroblastoma cells for chemotherapy by shifting the balance towards pro-apoptotic Bcl-2 proteins and enhanced mitochondrial apoptosis[J]. Oncogene, 2011, 30(4): 494-503.
LIN T A, WU V C, WANG C Y. Autophagy in chronic kidney diseases[J]. Cells, 2019, 8(1): 61.
KOCH E A T, NAKHOUL R, NAKHOUL F, et al. Autophagy in diabetic nephropathy: a review[J]. Int Urol Nephrol, 2020, 52(9): 1705-1712.
HE L, LIVINGSTON M J, DONG Z. Autophagy in acute kidney injury and repair[J]. Nephron Clin Pract, 2014, 127(1-4): 56-60.
CALNAN D R, BRUNET A. The FoxO code[J]. Oncogene, 2008, 27(16): 2276-2288.
EIJKELENBOOM A, BURGERING B M. FOXOs: signalling integrators for homeostasis maintenance[J]. Nat Rev Mol Cell Biol, 2013, 14(2): 83-97.
JUNG C H, RO S H, CAO J, et al. mTOR regulation of autophagy[J]. FEBS Lett, 2010, 584(7): 1287-1295.
LAPLANTE M, SABATINI D M. mTOR signaling at a glance[J]. J Cell Sci, 2009, 122(Pt 20): 3589-3594.
赵明明. 基于PI3K/AKT/mTOR及AMPK/mTOR通路调控自噬探讨加味黄芪赤风汤保护足细胞机制[D]. 北京:中国中医科学院,2022.
YANG F, QU Q, ZHAO C, et al. Paecilomyces cicadae-fermented Radix astragali activates podocyte autophagy by attenuating PI3K/AKT/mTOR pathways to protect against diabetic nephropathy in mice[J]. Biomed Pharmacother, 2020, 129: 110479.
何康婧,高增平,王晓雪,等. 基于PI3K/Akt/mTOR自噬信号通路研究雷公藤多苷片对糖尿病肾病大鼠肾脏损伤的保护作用[J]. 中南药学,2020, 18(6): 905-909.
LIU J, LIU S, PAN W, et al. Wogonoside attenuates the articular cartilage injury and the infiltration of Th1/Th2-type cytokines in papain-induced osteoarthritis in rat model via inhibiting the NF-κB and ERK1/2 activation[J]. Immunopharmacol Immunotoxicol, 2021, 43(3): 343-352.
李冰冰,于海波. 汉黄芩苷通过调节Nrf2/HO-1通路对大鼠心肌缺血再灌注(I/R)损伤的保护作用[J]. 广东化工,2021,48(7):37-40.
赵新. 汉黄芩苷对糖尿病大鼠肾组织炎症因子表达及TLR4/NF-κB信号通路的影响[J]. 中成药,2020, 42(8): 2166-2169.
SUN Q R, ZHANG X, FANG K. Phenotype of vascular smooth muscle cells (VSMCs) is regulated by miR-29b by targeting Sirtuin 1[J]. Med Sci Monit, 2018, 24: 6599-6607.
OU Y, ZHANG W, CHEN S, et al. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway[J]. Open Med (Wars), 2021, 16(1): 1286-1298.
黄琦,廖鑫,吴芹,等. 金钗石斛生物总碱对糖尿病大鼠血糖及肝脏组织IRS-2 mRNA,IGF-1 mRNA表达的影响[J]. 中国实验方剂学杂志,2014, 20(19): 155-158.
樊小宝,丁通,孙燕,等. 石斛碱对糖尿病肾病大鼠PI3K/Akt/mTOR信号通路及足细胞功能障碍的影响[J]. 河北医药,2021, 43(11):1631-1634, 1639.
PARSAMANESH N, MOOSSAVI M, BAHRAMI A, et al. Therapeutic potential of curcumin in diabetic complications[J]. Pharmacol Res, 2018, 136: 181-193.
TU Q, LI Y, JIN J, et al. Curcumin alleviates diabetic nephropathy via inhibiting podocyte mesenchymal transdifferentiation and inducing autophagy in rats and MPC5 cells[J]. Pharm Biol, 2019, 57(1): 778-786.
SU P, DU S, LI H, et al. Notoginsenoside R1 inhibits oxidized low-density lipoprotein induced inflammatory cytokines production in human endothelial EA.hy926 cells[J]. Eur J Pharmacol, 2016, 770: 9-15.
YU Y, SUN G, LUO Y, et al. Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress-related signaling pathways[J]. Sci Rep, 2016, 6: 21730.
HUANG G, ZOU B, LV J, et al. Notoginsenoside R1 attenuates glucose-induced podocyte injury via the inhibition of apoptosis and the activation of autophagy through the PI3K/Akt/mTOR signaling pathway[J]. Int J Mol Med, 2017, 39(3): 559-568.
KIM T W, SONG I B, LEE H K, et al. Platycodin D, a triterpenoid sapoinin from Platycodon grandiflorum, ameliorates cisplatin-induced nephrotoxicity in mice[J]. Food Chem Toxicol, 2012, 50(12): 4254-4259.
吴浩,符丽珍,赵勇,等. 桔梗皂苷D通过介导PI3K/Akt/mTOR信号通路调节氧化应激改善糖尿病肾病模型大鼠肾损伤[J]. 中国药理学与毒理学杂志,2022, 36(3): 170-176.
王晓伟,余小柱,郭二霞,等. 蛇床子素通过PI3K/Akt/mTOR通路对糖尿病肾病大鼠纤维化及HSP90、SIRT1的影响[J]. 中国老年学杂志,2023, 43(6): 1446-1450.
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