中药靶向PI3K/Akt/mTOR通路调节自噬在糖尿病肾脏病中的研究进展

doi:10.3969/j.issn.1004-583X.2023.06.016

摘要/Abstract

摘要：

糖尿病肾脏病(diabetic kidney disease,DKD)是由机体糖、脂代谢紊乱引起的肾小球病变。DKD患者自噬相关蛋白表达减少,肾小球足细胞生理功能丧失。磷脂酰肌醇激酶(phosphatidyl inositol 3-kinase, PI3K)/蛋白激酶B(protein kinase B, PKB/Akt)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路通过激活自噬,可清除病原体及细胞内衰老损伤的细胞器,调节细胞周期与能量代谢,减少氧化应激给足细胞带来的不可逆损伤,减缓DKD患者的肾功能恶化。本文通过对中药靶向PI3K/Akt/mTOR通路调节自噬在DKD中的研究现况进行综述,旨在为DKD的早期干预和药物研发开拓新思路。

关键词: 糖尿病肾病, PI3K/Akt/mTOR, 足细胞, 自噬

中图分类号:

R587.24

陈婷, 刘金彦. 中药靶向PI3K/Akt/mTOR通路调节自噬在糖尿病肾脏病中的研究进展[J]. 临床荟萃, 2023, 38(6): 564-568.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2023.06.016

https://huicui.hebmu.edu.cn/CN/Y2023/V38/I6/564

图/表 1

参考文献 54

[1]	Warren AM, Knudsen ST, Cooper ME. Diabetic nephropathy: An insight into molecular mechanisms and emerging therapies[J]. Expert Opin Ther Targets, 2019, 23(7):579-591. doi: 10.1080/14728222.2019.1624721 URL
[2]	Gödel M, Hartleben B, Herbach N, et al. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice[J]. J Clin Invest, 2011, 121(6):2197-2209. doi: 10.1172/JCI44774 pmid: 21606591
[3]	Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J]. Diabetes Res Clin Pract, 2022, 183:109119. doi: 10.1016/j.diabres.2021.109119 URL
[4]	Yang D, Livingston MJ, Liu Z, et al. Autophagy in diabetic kidney disease: Regulation, pathological role and therapeutic potential[J]. Cell Mol Life Sci, 2018, 75(4):669-688. doi: 10.1007/s00018-017-2639-1 pmid: 28871310
[5]	Aboolian A, Urner S, Roden M, et al. Diabetic kidney disease: From pathogenesis to novel treatment possibilities[J]. Handb Exp Pharmacol, 2022, 274:269-307. doi: 10.1007/164_2021_576 pmid: 35318511
[6]	Pereira PR, Carrageta DF, Oliveira PF, et al. Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease[J]. Med Res Rev, 2022, 42(4):1518-1544. doi: 10.1002/med.21883 pmid: 35274315
[7]	中华医学会糖尿病学分会微血管并发症学组. 中国糖尿病肾脏病防治指南(2021年版)[J]. 国际内分泌代谢杂志, 2021, 41(4):388-410.
[8]	Tang C, Livingston MJ, Liu Z, et al. Autophagy in kidney homeostasis and disease[J]. Nat Rev Nephrol, 2020, 16(9):489-508. doi: 10.1038/s41581-020-0309-2 pmid: 32704047
[9]	Wong SQ, Kumar AV, Mills J, et al. Autophagy in aging and longevity[J]. Hum Genet, 2020, 139(3):277-290. doi: 10.1007/s00439-019-02031-7 pmid: 31144030
[10]	Lin Q, Banu K, Ni Z, et al. Podocyte autophagy in homeostasis and disease[J]. J Clin Med, 2021, 10(6):1184. doi: 10.3390/jcm10061184 URL
[11]	Li W, He P, Huang Y, et al. Selective autophagy of intracellular organelles: Recent research advances[J]. Theranostics, 2021, 11(1):222-256. doi: 10.7150/thno.49860 pmid: 33391472
[12]	Cao W, Li J, Yang K, et al. An overview of autophagy: Mechanism, regulation and research progress[J]. Bull Cancer, 2021, 108(3):304-322. doi: 10.1016/j.bulcan.2020.11.004 pmid: 33423775
[13]	Koch EAT, Nakhoul R, Nakhoul F, et al. Autophagy in diabetic nephropathy: A review[J]. Int Urol Nephrol, 2020, 52(9):1705-1712. doi: 10.1007/s11255-020-02545-4 pmid: 32661628
[14]	Fogo AB. Gains in understanding of podocyte loss[J]. Kidney Int, 2021, 100(5):978-980. doi: 10.1016/j.kint.2021.08.003 pmid: 34688386
[15]	Shankland SJ, Wang Y, Shaw AS, et al. Podocyte aging: Why and how getting old matters[J]. J Am Soc Nephrol, 2021, 32(11):2697-2713. doi: 10.1681/ASN.2021050614 pmid: 34716239
[16]	Tagawa A, Yasuda M, Kume S, et al. Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy[J]. Diabetes, 2016, 65(3):755-767. doi: 10.2337/db15-0473 pmid: 26384385
[17]	Kume S, Maegawa H. Lipotoxicity, nutrient-sensing signals, and autophagy in diabetic nephropathy[J]. JMA J, 2020, 3(2):87-94.
[18]	Bharath LP, Rockhold JD, Conway R. Selective autophagy in hyperglycemia-induced microvascular and macrovascular diseases[J]. Cells, 2021, 10(8): 2114. doi: 10.3390/cells10082114 URL
[19]	Mahtal N, Lenoir O, Tharaux PL. Glomerular endothelial cell crosstalk with podocytes in diabetic kidney disease[J]. Front Med (Lausanne), 2021, 8:659013.
[20]	Ballermann BJ, Nyström J, Haraldsson B. The glomerular endothelium restricts albumin filtration[J]. Front Med (Lausanne), 2021, 8:766689.
[21]	钱子冰, 刘静, 曾佩芸, 等. mTOR调控自噬参与糖尿病并发症的研究进展[J]. 基础医学与临床, 2021, 41(8):1200-1204.
[22]	陈婷, 刘金彦. PI3K/Akt/mTOR通路与足细胞自噬在糖尿病肾病肾功能修复中的研究[J]. 医学信息, 2022, 35(22):170-175.
[23]	Miricescu D, Totan A, Stanescu-Spinu II, et al. PI3K/AKT/mTOR signaling pathway in breast cancer: From molecular landscape to clinical aspects[J]. Int J Mol Sci, 2020, 22(1): 173. doi: 10.3390/ijms22010173 URL
[24]	Xu Z, Jia K, Wang H, et al. METTL14-regulated PI3K/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial-mesenchymal transition of renal tubular cells in diabetic kidney disease[J]. Cell Death Dis, 2021, 12(1):32. doi: 10.1038/s41419-020-03312-0 pmid: 33414476
[25]	Yin H, Zuo Z, Yang Z, et al. Nickel induces autophagy via PI3K/AKT/mTOR and AMPK pathways in mouse kidney[J]. Ecotoxicol Environ Saf, 2021, 223:112583. doi: 10.1016/j.ecoenv.2021.112583 URL
[26]	Chen Y, Zheng Y, Lin X, et al. Dendrobium mixture attenuates renal damage in rats with diabetic nephropathy by inhibiting the PI3K/Akt/mTOR pathway[J]. Mol Med Rep, 2021, 24(2):590. doi: 10.3892/mmr URL
[27]	Shiau JP, Chuang YT, Cheng YB, et al. Impacts of oxidative stress and PI3K/AKT/mTOR on metabolism and the future direction of investigating fucoidan-modulated metabolism[J]. Antioxidants (Basel), 2022, 11(5): 911.
[28]	Nitulescu G, Van De Venter M, Nitulescu G, et al. The Akt pathway in oncology therapy and beyond (Review)[J]. Int J Oncol, 2018, 53(6):2319-2331. doi: 10.3892/ijo.2018.4597 pmid: 30334567
[29]	Jin J, Gong J, Zhao L, et al. LncRNA Hoxb3os protects podocytes from high glucose-induced cell injury through autophagy dependent on the Akt-mTOR signaling pathway[J]. Acta Biochim Pol, 2021, 68(4):619-625. doi: 10.18388/abp.2020_5483 pmid: 34648253
[30]	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.
[31]	Wang Y. Traditional uses, chemical constituents, pharmacological activities, and toxicological effects of Dendrobium leaves: A review[J]. J Ethnopharmacol, 2021, 270:113851. doi: 10.1016/j.jep.2021.113851 URL
[32]	马丽华, 朱虹, 李永. 铁皮石斛提取物治疗糖尿病肾病的临床观察[J]. 中国保健营养, 2020, 30 (17):60.
[33]	李毓扬, 吕承豪, 吴广, 等. 铁皮石斛干预代谢综合征的作用分子机制研究进展[J]. 中国中药杂志, 2019, 44(23):5102-5108.
[34]	王静. 铁皮石斛提取物治疗糖尿病肾病的临床研究[J]. 特别健康, 2022, (14):85-87.
[35]	常帅, 徐晓琴, 相华, 等. 雷公藤多苷通过Akt/mTOR信号通路对糖尿病肾病小鼠肾损伤的影响[J]. 河北医药, 2021, 43(1):25-29.
[36]	于向慧, 何艳玲, 杨雨菲, 等. 雷公藤多苷通过PI3K/Akt通路对糖尿病肾病大鼠热休克蛋白90及PGC-1α表达的影响[J]. 中国现代医学杂志, 2021, 31(22):10-16.
[37]	程亚清, 曲海顺, 张献之, 等. 雷公藤多苷辅助治疗糖尿病肾病的Meta分析[J]. 中国中西医结合肾病杂志, 2022, 23(2):133-139.
[38]	杨丽, 庞洁玉, 段雪萍, 等. 雷公藤多苷治疗糖尿病肾脏疾病作用机制概述[J]. 实用中医药杂志, 2022, 38(6):1069-1072.
[39]	姚琼, 叶太生, 张莹雯, 等. 基于网络药理学及Akt1/mTOR自噬通路探讨黄芪减少糖尿病肾病蛋白尿的作用机制[J]. 世界科学技术-中医药现代化, 2021, 23(8):2699-2710.
[40]	张永选. 黄芪注射液治疗对糖尿病肾病患者血清TGF-β1、VEGF水平的影响分析[J]. 四川解剖学杂志, 2021, 29(1):175-176.
[41]	刘婕. 中药黄芪治疗糖尿病肾病患者的效果观察[J]. 现代诊断与治疗, 2022, 33(1):21-24.
[42]	Tang G, Li S, Zhang C, et al. Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management[J]. Acta Pharm Sin B, 2021, 11(9):2749-2767. doi: 10.1016/j.apsb.2020.12.020 pmid: 34589395
[43]	李小芳, 黄海平, 杨剑, 等. 黄芪补肾活血汤联合西医疗法治疗早期糖尿病肾病的疗效及对患者肾功能的影响研究[J]. 贵州医药, 2022, 46(2):209-210.
[44]	薛守宇, 廉婷, 耿爱民, 等. 黄芪熟黄散瘀方联合维格列汀与缬沙坦治疗早期糖尿病肾病疗效及对患者血糖和肾功能水平的影响[J]. 陕西中医, 2022, 43(2):207-210.
[45]	郭维文. 黄芪益肾颗粒对早期糖尿病肾病患者肾功能的影响[J]. 按摩与康复医学, 2022, 13(11):21-24.
[46]	Xu C, Wang W, Wang B, et al. Analytical methods and biological activities of Panax notoginseng saponins: Recent trends[J]. J Ethnopharmacol, 2019, 236:443-465. doi: S0378-8741(18)31808-7 pmid: 30802611
[47]	Guo X, Sun W, Luo G, et al. Panax notoginseng saponins alleviate skeletal muscle insulin resistance by regulating the IRS1-PI3K-AKT signaling pathway and GLUT4 expression[J]. FEBS Open Bio, 2019, 9(5):1008-1019. doi: 10.1002/2211-5463.12635 pmid: 30945455
[48]	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]. FEBS Open Bio, 2017, 39(3):559-568.
[49]	Gui D, Wei L, Jian G, et al. Notoginsenoside R1 ameliorates podocyte adhesion under diabetic condition through alpha3beta1 integrin upregulation in vitro and in vivo[J]. Cell Physiol Biochem, 2014, 34(6):1849-1862. doi: 10.1159/000366384 URL
[50]	Tang X, Huang M, Jiang J, et al. Panax notoginseng preparations as adjuvant therapy for diabetic kidney disease: a systematic review and meta-analysis[J]. Pharm Biol, 2020, 58(1):138-145. doi: 10.1080/13880209.2020.1711782 pmid: 31967924
[51]	Han J, Zhang Y, Shi X, et al. Tongluo Digui decoction treats renal injury in diabetic rats by promoting autophagy of podocytes[J]. J Tradit Chin Med, 2021, 41(1):125-132. doi: 10.19852/j.cnki.jtcm.2021.01.014 pmid: 33522205
[52]	庞欣欣, 石秀杰, 张雅歌, 等. 通络地龟汤治疗2型糖尿病肾病Ⅳ期患者的临床疗效研究[J]. 中国全科医学, 2020, 23(30):3846-3850. doi: 10.12114/j.issn.1007-9572.2020.00.267
[53]	韩佳瑞, 张雅歌, 石秀杰, 等. 通络地龟汤对糖尿病肾病小鼠肾脏NLRP3炎症小体及炎症因子表达的影响[J]. 中药材, 2021, 44(4):943-948.
[54]	庞欣欣, 石秀杰, 张雅歌, 等. 通络地龟汤对糖尿病肾病Ⅳ期患者非杓型血压和尿钠排泄及肾素-血管紧张素-醛固酮系统的影响研究[J]. 中国全科医学, 2021, 24(15):1943-1950, 1958. doi: 10.12114/j.issn.1007-9572.2021.00.079

中药靶向PI3K/Akt/mTOR通路调节自噬在糖尿病肾脏病中的研究进展

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 1

参考文献 54

相关文章 15

编辑推荐

Metrics

本文评价

[1]	李会芳, 苗霞. 甲状腺激素水平对2型糖尿病肾脏病风险的预测[J]. 临床荟萃, 2023, 38(2): 137-142.
[2]	王翠, 林昊, 武萍萍, 张雅丽, 任建, 徐婷, 董国玉, 宰国田. 2型糖尿病患者高同型半胱氨酸血症与早期肾脏疾病的相关性[J]. 临床荟萃, 2023, 38(1): 42-45.
[3]	姚瑶, 褚敏. 糖尿病肾病患者认知功能障碍与血清β淀粉样蛋白的关系[J]. 临床荟萃, 2022, 37(9): 813-816.
[4]	程霞, 程兰兰, 张鹏伟, 马志刚. 钠-葡萄糖协同转运蛋白2抑制剂肾脏保护作用的研究进展[J]. 临床荟萃, 2022, 37(5): 467-471.
[5]	高士欣, 宋冰, 施克新. 血清脂蛋白α、胱抑素-C和尿酸检测对早期糖尿病肾病的诊断价值[J]. 临床荟萃, 2022, 37(3): 248-252.
[6]	杜菲, 李英. 老年糖尿病肾病患者肠道菌群失调的研究进展[J]. 临床荟萃, 2022, 37(2): 178-181.
[7]	贺枫, 牛璐, 雒杲, 杨睿斐, 李凡凡, 成晓琼, 安斌斌, 李京娟, 刘媛媛, 郭茜, 王金羊. 中国人内脏脂肪指数及内脏脂肪面积与糖尿病肾病的相关性及其预警价值[J]. 临床荟萃, 2022, 37(12): 1089-1093.
[8]	刘猛, 胡桂才, 杨宗娜, 郭伟伟, 陈万欣. 糖尿病肾脏疾病与非糖尿病肾脏疾病血液透析患者容量负荷与营养状况的比较[J]. 临床荟萃, 2021, 36(4): 332-335.
[9]	刘伦志, 邓璐, 张明霞. 血管紧张素Ⅱ1型受体拮抗剂对早期糖尿病肾病患者尿液中足细胞相关蛋白nephrin、自噬基因Beclin-1 mRNA排泄的影响[J]. 临床荟萃, 2021, 36(11): 1005-1008.
[10]	沈琰, 黄诗纯, 陈怡, 詹明. 焦虑和抑郁心理状态对糖尿病肾病影响的研究进展[J]. 临床荟萃, 2021, 36(11): 1029-1033.
[11]	武肖珊, 李英. 钠-葡萄糖协同转运蛋白2抑制剂对糖尿病肾病保护作用的研究进展[J]. 临床荟萃, 2021, 36(11): 1034-1040.
[12]	王亚丽, 王瑞英, 崔月. 2型糖尿病患者尿白蛋白与葡萄糖负荷后2小时血糖增值的关系[J]. 临床荟萃, 2021, 36(1): 49-53.
[13]	梁欢1，刘建凤2. 盘点钠-葡萄糖协同转运蛋白2抑制剂临床研究新进展[J]. 临床荟萃, 2020, 35(9): 861-864.
[14]	马光宇1，付冰冰2，孙晓鹏2. 细胞自噬与狼疮肾炎研究进展[J]. 临床荟萃, 2020, 35(7): 662-666.
[15]	姜雯雯1，宋雅伟2，祁媚姣1，李小娟3，刘玉梅1. NGAL、炎症细胞因子在2型糖尿病肾脏疾病患者体内的变化[J]. 临床荟萃, 2020, 35(3): 238-241.