|
|
基于PI3K/Akt/mTOR通路探讨中医药治疗IgA肾病的研究进展
|
Abstract:
免疫球蛋白A (IgA)肾病是最常见的原发性肾小球疾病，是导致终末期肾脏病的关键原因之一。IgA肾病发病机制十分复杂多样，磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B (PKB，又称Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路是细胞内一条至关重要的信号通路，与IgA肾病的发生发展密不可分。近年来，中医药在防治IgA肾病方面的研究逐渐深入，展现了中医药的独特优势。基于中医药治疗IgA肾病的现状，本文参考了近几年国内外文献，探讨了PI3K/Akt/mTOR信号通路在IgA肾病中的调控作用及中医药基于该通路对IgA肾病的作用，以期为中医药防治IgA肾病提供新思路。
Immunoglobulin A (IgA) nephropathy is the most common primary glomerular disease and one of the key causes of end-stage renal disease. The pathogenesis of IgA nephropathy is very complex and diverse. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, also known as Akt)/mammalian rapamycin target protein (mTOR) signaling pathway is a crucial intracellular signaling pathway that is closely related to the occurrence and development of IgA nephropathy. In recent years, research on traditional Chinese medicine in the prevention and treatment of IgA nephropathy has gradually deepened, demonstrating the unique advantages of traditional Chinese medicine. Based on the current situation of traditional Chinese medicine treatment for IgA nephropathy, this article refers to recent domestic and foreign literature to explore the regulatory role of the PI3K/Akt/mTOR signaling pathway in IgA nephropathy and the effect of traditional Chinese medicine on IgA nephropathy based on this pathway, in order to provide new ideas for the prevention and treatment of IgA nephropathy with traditional Chinese medicine.
| [1] | 王苗苗, 刘超. 原发性IgA肾病病因病机探析[J]. 中国现代医药杂志, 2019, 21(5): 96-97. |
| [2] | 王英杰, 米焱, 王彩丽. IgA肾病中补体甘露糖结合凝集素途径相关分子研究进展[J]. 现代免疫学, 2023, 43(2): 175-180. |
| [3] | 杨惠婷, 蔡泽霖, 陈洪宇. 陈洪宇教授防治IgA肾病合并急性上呼吸道感染经验[J]. 中国中西医结合肾病杂志, 2023, 24(6): 477-479. |
| [4] | 赵芃博, 纪越, 齐鑫, 等. IgA肾病中西医发病机制及诊治进展[J]. 中医药学报, 2023, 51(9): 97-103. |
| [5] | 许超, 夏虹, 邓跃毅. 健脾补肾通络法联合强的松治疗进展型IgA肾病的效果[J]. 中国医药导报, 2020, 17(18): 87-90. |
| [6] | 李锦青, 王奕, 马晓燕, 等. IgA肾病的中西医结合治疗新进展[J]. 中国中西医结合肾病杂志, 2024, 25(3): 264-267. |
| [7] | 刘晓羽, 黄志敏, 邱少彬, 等. 三七调节肾脏PI3K/Akt/mTORC1-线粒体能量代谢治疗血瘀证慢性肾衰竭大鼠的机制研究 [J]. 中国中药杂志, 2024, 49(7): 1888-1895. |
| [8] | Yang, J., Pi, C. and Wang, G. (2018) Inhibition of PI3K/Akt/mTOR Pathway by Apigenin Induces Apoptosis and Autophagy in Hepatocellular Carcinoma Cells. Biomedicine & Pharmacotherapy, 103, 699-707. https://doi.org/10.1016/j.biopha.2018.04.072 |
| [9] | Glaviano, A., Foo, A.S.C., Lam, H.Y., Yap, K.C.H., Jacot, W., Jones, R.H., et al. (2023) PI3K/AKT/mTOR Signaling Transduction Pathway and Targeted Therapies in Cancer. Molecular Cancer, 22, Article No. 138. https://doi.org/10.1186/s12943-023-01827-6 |
| [10] | Vanhaesebroeck, B., Whitehead, M.A. and Piñeiro, R. (2015) Molecules in Medicine Mini-Review: Isoforms of PI3K in Biology and Disease. Journal of Molecular Medicine, 94, 5-11. https://doi.org/10.1007/s00109-015-1352-5 |
| [11] | 席建宏, 黄柯婷, 王志旺, 等. PI3K/Akt信号通路调控哮喘气道黏液高分泌的研究现状[J]. 中国临床药理学杂志, 2022, 38(22): 2779-2782. |
| [12] | Long, H., Cheng, Y., Zhou, Z., Luo, H., Wen, D. and Gao, L. (2021) PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease. Frontiers in Pharmacology, 12, Article ID: 648636. https://doi.org/10.3389/fphar.2021.648636 |
| [13] | Manning, B.D. and Toker, A. (2017) AKT/PKB Signaling: Navigating the Network. Cell, 169, 381-405. https://doi.org/10.1016/j.cell.2017.04.001 |
| [14] | Liu, G.Y. and Sabatini, D.M. (2020) mTOR at the Nexus of Nutrition, Growth, Ageing and Disease. Nature Reviews Molecular Cell Biology, 21, 183-203. https://doi.org/10.1038/s41580-019-0199-y |
| [15] | Mao, B., Zhang, Q., Ma, L., Zhao, D., Zhao, P. and Yan, P. (2022) Overview of Research into mTOR Inhibitors. Molecules, 27, Article No. 5295. https://doi.org/10.3390/molecules27165295 |
| [16] | Acosta-Martinez, M. and Cabail, M.Z. (2022) The PI3k/Akt Pathway in Meta-Inflammation. International Journal of Molecular Sciences, 23, Article No. 15330. https://doi.org/10.3390/ijms232315330 |
| [17] | Guo, H., German, P., Bai, S., Barnes, S., Guo, W., Qi, X., et al. (2015) The PI3K/AKT Pathway and Renal Cell Carcinoma. Journal of Genetics and Genomics, 42, 343-353. https://doi.org/10.1016/j.jgg.2015.03.003 |
| [18] | Luan, R., Tian, G., Ci, X., Zheng, Q., Wu, L. and Lu, X. (2021) Differential Expression Analysis of Urinary Exosomal Circular RNAs in Patients with Iga Nephropathy. Nephrology, 26, 432-441. https://doi.org/10.1111/nep.13855 |
| [19] | Xu, Y., Ling, Y., Yang, F., Deng, J., Rong, L., Jiang, M., et al. (2017) The mTOR/p70s6k1 Signaling Pathway in Renal Fibrosis of Children with Immunoglobulin a Nephropathy. Journal of the Renin-Angiotensin-Aldosterone System, 18, 3. https://doi.org/10.1177/1470320317717831 |
| [20] | 张春江, 赵丹, 陈志刚, 等. PI3K/Akt/mTOR信号通路对大鼠肾小球系膜细胞增殖的调控作用探讨[J]. 内科急危重症杂志, 2016, 22(4): 308-311. |
| [21] | Tang, C., Livingston, M.J., Liu, Z. and Dong, Z. (2020) Autophagy in Kidney Homeostasis and Disease. Nature Reviews Nephrology, 16, 489-508. https://doi.org/10.1038/s41581-020-0309-2 |
| [22] | Lv, X., Wang, J., Zhang, L., Shao, X., Lin, Y., Liu, H., et al. (2022) Canagliflozin Reverses Th1/Th2 Imbalance and Promotes Podocyte Autophagy in Rats with Membranous Nephropathy. Frontiers in Immunology, 13, Article ID: 993869. https://doi.org/10.3389/fimmu.2022.993869 |
| [23] | Tan, X., Liu, Y., Liu, D., Tang, X., Xia, M., Chen, G., et al. (2022) SUMO1 Promotes Mesangial Cell Proliferation through Inhibiting Autophagy in a Cell Model of IgA Nephropathy. Frontiers in Medicine, 9, Article ID: 834164. https://doi.org/10.3389/fmed.2022.834164 |
| [24] | Wang, L. and Law, H.K.W. (2018) Immune Complexes Suppressed Autophagy in Glomerular Endothelial Cells. Cellular Immunology, 328, 1-8. https://doi.org/10.1016/j.cellimm.2018.02.013 |
| [25] | Shi, B., Ma, M., Zheng, Y., Pan, Y. and Lin, X. (2019) mTOR and Beclin1: Two Key Autophagy‐Related Molecules and Their Roles in Myocardial Ischemia/reperfusion Injury. Journal of Cellular Physiology, 234, 12562-12568. https://doi.org/10.1002/jcp.28125 |
| [26] | Jia, M., Qiu, H., Lin, L., Zhang, S., Li, D. and Jin, D. (2022) Inhibition of PI3K/AKT/mTOR Signalling Pathway Activates Autophagy and Suppresses Peritoneal Fibrosis in the Process of Peritoneal Dialysis. Frontiers in Physiology, 13, Article ID: 778479. https://doi.org/10.3389/fphys.2022.778479 |
| [27] | Yeo, S.C., Cheung, C.K. and Barratt, J. (2017) New Insights into the Pathogenesis of IgA Nephropathy. Pediatric Nephrology, 33, 763-777. https://doi.org/10.1007/s00467-017-3699-z |
| [28] | 张广发, 蔡颖莹, 林龙, 等. 基于PI3K/AKT/mTOR信号通路探讨大黄煎剂对轻微型肝性脑病大鼠脑组织炎症损伤的保护机制[J]. 临床肝胆病杂志, 2024, 40(2): 312-318. |
| [29] | Deretic, V. (2021) Autophagy in Inflammation, Infection, and Immunometabolism. Immunity, 54, 437-453. https://doi.org/10.1016/j.immuni.2021.01.018 |
| [30] | Hu, Y., Wang, S., Wu, F., Wu, K., Shi, R., Qin, L., et al. (2022) Effects and Mechanism of Ganoderma lucidum Polysaccharides in the Treatment of Diabetic Nephropathy in Streptozotocin‐Induced Diabetic Rats. BioMed Research International, 2022, Article ID: 4314415. https://doi.org/10.1155/2022/4314415 |
| [31] | Liu, D., Liu, Y., Chen, G., He, L., Tang, C., Wang, C., et al. (2017) Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy. American Journal of Nephrology, 45, 293-300. https://doi.org/10.1159/000456039 |
| [32] | 刘童童, 占永立, 冒慧敏. 半夏泻心汤治疗IgA肾病的理论及研究基础[J]. 中国中西医结合肾病杂志, 2019, 20(9): 834-836. |
| [33] | 陈香美, 邓跃毅, 谢院生. IgA肾病西医诊断和中医辨证分型的实践指南[J]. 中国中西医结合杂志, 2013, 33(5): 583-585. |
| [34] | 万佩君, 鲁凌飞, 熊国良. 熊国良辨治IgA肾病用药规律分析[J]. 亚太传统医药, 2023, 19(7): 157-162. |
| [35] | 朱勤, 陈洪宇, 曾佳丽, 等. 王永钧教授新五型辨证论治IgA肾病技巧赏析[J]. 中国中西医结合肾病杂志, 2023, 24(10): 850-852. |
| [36] | 卢程程, 王东, 王亿平. 中医药治疗IgA肾病研究进展[J]. 陕西中医学院学报, 2022(4): 45. |
| [37] | 王宏安, 刘艳华, 张守琳. 任继学从“毒损肾络”论治IgA肾病[J]. 长春中医药大学学报, 2022, 38(8): 851-853. |
| [38] | 袁铭依, 朱彩凤, 包自阳. 朱彩凤运用“魄门亦为五脏使”理论治疗IgA肾病经验[J]. 浙江中医杂志, 2022, 57(2): 92-93. |
| [39] | 卫若楠, 于同月. 雷公藤的临床应用及其用量探究[J]. 长春中医药大学学报, 2022, 38(5): 491-494. |
| [40] | 何康婧, 高增平, 尹丽梅, 等. 雷公藤多苷的药理毒理作用研究进展[J]. 中国实验方剂学杂志, 2020, 26(1): 196-204. |
| [41] | Liang, S., Jin, J., Shen, X., Jiang, X., Li, Y. and He, Q. (2018) Triptolide Protects Podocytes via Autophagy in Immunoglobulin a Nephropathy. Experimental and Therapeutic Medicine, 16, 2275-2280. https://doi.org/10.3892/etm.2018.6480 |
| [42] | 马艳春, 胡建辉, 吴文轩, 等. 黄芪化学成分及药理作用研究进展[J]. 中医药学报, 2022, 50(4): 92-95. |
| [43] | Lu, R., Chen, J., Liu, B., Lin, H., Bai, L., Zhang, P., et al. (2020) Protective Role of Astragaloside IV in Chronic Glomerulonephritis by Activating Autophagy through PI3K/AKT/AS160 Pathway. Phytotherapy Research, 34, 3236-3248. https://doi.org/10.1002/ptr.6772 |
| [44] | 彭胜男, 陶琰心, 洪婷. 黄芪甲苷通过mTORC1通路调控IgA肾病大鼠脾淋巴细胞分化[J]. 中国免疫学杂志, 2021, 37(4): 421-425. |
| [45] | 冯科冉, 李伟霞, 王晓艳, 等. 丹参化学成分､药理作用及其质量标志物(Q-Marker)的预测分析[J]. 中草药, 2022, 53(2): 609-618. |
| [46] | 孙兰, 田平平, 张帆, 等. 丹酚酸B对高糖诱导的大鼠肾小管上皮细胞转分化的影响及机制研究[J]. 中国中药杂志, 2020, 45(16): 3922-3930. |
| [47] | Chen, J., Yuan, S., Zhou, J., Huang, X., Wu, W., Cao, Y., et al. (2022) Danshen Injection Induces Autophagy in Podocytes to Alleviate Nephrotic Syndrome via the PI3K/AKT/mTOR Pathway. Phytomedicine, 107, Article ID: 154477. https://doi.org/10.1016/j.phymed.2022.154477 |
| [48] | 汪晓河, 马明华, 张婧婷, 等. 青蒿药理作用研究进展[J]. 中国现代应用药学, 2018, 35(5): 781-785. |
| [49] | Xia, M., Liu, D., Tang, X., Liu, Y., Liu, H., Liu, Y., et al. (2020) Dihydroartemisinin Inhibits the Proliferation of IgAN Mesangial Cells through the mTOR Signaling Pathway. International Immunopharmacology, 80, Article ID: 106125. https://doi.org/10.1016/j.intimp.2019.106125 |
| [50] | 范沐霞, 赵塔娜, 王丽敏, 等. 姜黄素抗纤维化研究进展[J]. 中医学报, 2019, 34(11): 2343-2348. |
| [51] | Lu, M., Li, H., Liu, W., Zhang, X., Li, L. and Zhou, H. (2021) Curcumin Attenuates Renal Interstitial Fibrosis by Regulating Autophagy and Retaining Mitochondrial Function in Unilateral Ureteral Obstruction Rats. Basic & Clinical Pharmacology & Toxicology, 128, 594-604. https://doi.org/10.1111/bcpt.13550 |
| [52] | 马旺霞, 王斌. 通络药水蛭及配伍防治糖尿病肾病的机制探析[J]. 中医临床研究, 2024, 16(18): 61-66. |
| [53] | 曹响, 谢丽萍, 赵洁, 等. 基于PI3K/Akt/mTOR通路探讨水蛭对IgA肾病的作用机制[J]. 亚太传统医药, 2020, 16(2): 181-184. |
| [54] | 陈明, 田锋, 吴宸广, 等. 基于“三脏三腑-黏膜轴”理论探讨肾炎止血丸治疗IgA肾病的作用机制[J]. 中国中西医结合肾病杂志, 2022, 23(3): 272-273. |
| [55] | 陈明, 王立范, 于卓, 等. 基于网络药理学探讨肾炎止血丸治疗IgA肾病的作用机制[J]. 中国中西医结合肾病杂志, 2023, 24(2): 137-141+192. |
| [56] | 李珺, 王高强, 岳艳利, 等. 实脾固肾化瘀方对CKD-MBD脾肾气虚证患者血清FGF23的影响[J]. 中医药学报, 2019, 47(5): 63-66. |
| [57] | 王卓媛, 杨柳易, 苟小军, 等. 基于网络药理学及分子对接技术探讨实脾固肾化瘀方治疗IgA肾病的作用机制[J]. 中药新药与临床药理, 2022, 33(11): 1528-1535. |
| [58] | 张圆圆, 靳培培, 靳贺超, 等. 基于C1GALT1/C1GALT1C1通路探讨加味升降散对IgA肾病大鼠Gd-IgA1的影响 [J]. 中国实验方剂学杂志, 2022, 28(14): 70-80. |
| [59] | 张圆圆, 靳培培, 顾悦, 等. 基于网络药理学､分子对接及实验验证探讨加味升降散治疗IgA肾病的作用机制[J]. 中国实验方剂学杂志, 2022, 28(7): 162-171. |
| [60] | 翟文生, 杨濛, 李前前, 等. 益气化瘀清热方及其拆方对大鼠肾小球系膜细胞TGF-βRⅠmRNA及其蛋白的影响[J]. 中华中医药学刊, 2017, 35(9): 2215-2218. |
| [61] | 何改丽, 李冰, 赵永旺, 等. 益气化瘀清热方及其拆方对IgA肾病大鼠肾组织mTOR信号通路的影响[J]. 中华中医药杂志, 2018, 33(10): 4727-4730. |
| [62] | 翟文生, 赵永旺. 益气化瘀清热方及其拆方对IgA肾病大鼠肾组织病理及其表达Nephrin、Podocin蛋白的影响[J]. 中华中医药杂志, 2019, 34(10): 4888-4892. |
| [63] | 李亚飞. 河洛文化视野下六味地黄丸组方思想诠释[J]. 中医学报, 2023, 38(4): 704-710. |
| [64] | Zhu, X., Shen, X., Lin, B., Fang, J., Jin, J. and He, Q. (2022) Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate Iga Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion. Frontiers in Pharmacology, 13, Article ID: 889008. https://doi.org/10.3389/fphar.2022.889008 |
| [65] | 吴鑫宇, 曲苗, 宋寒冰, 等. 大补阴丸对糖尿病肾病小鼠肾功能改善作用研究[J]. 中医药学报, 2022, 50(2): 39-43. |
| [66] | 顾一凡, 卢志钦, 李雨珊, 等. 基于网络药理学探讨大补阴丸治疗IgA肾病的作用机制[J]. 中国医药科学, 2024, 14(11): 74-78. |
| [67] | 于梅, 宋宁宁, 张雪枫, 等. 参芪地黄汤守法思变治疗慢性肾脏病显效1例[J]. 中国中西医结合肾病杂志, 2023, 24(3): 254-255. |
| [68] | 李鸣, 李亮, 李伟男, 等. 参芪地黄汤治疗IgA肾病作用机制的网络药理学研究[J]. 中国医药导报, 2021, 18(29): 8-13+197-198. |
