• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

达沙替尼增强肥胖小鼠肾脏中的自噬通量，抑制细胞凋亡，减少巨噬细胞浸润。

Enhanced Autophagic Flux, Suppressed Apoptosis and Reduced Macrophage Infiltration by Dasatinib in Kidneys of Obese Mice.

机构信息

Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.

Department of Anatomy, Faculty of Medicine, Horus University, New Damietta 34517, Egypt.

出版信息

Cells. 2022 Feb 21;11(4):746. doi: 10.3390/cells11040746.

DOI:10.3390/cells11040746
PMID:35203394
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8869974/
Abstract

Obesity causes renal changes (ORC), characterized by defective renal autophagy, lipogenesis, enhanced macrophage infiltration and apoptosis. We hypothesize that Dasatinib, a tyrosine kinase inhibitor, may ameliorate changes associated with obesity. We the mice with either Obesogenic diet (OD) or a standard basal diet. After 12 weeks, the mice received either vehicle or Dasatinib 4 mg/kg/d for an additional four weeks. We examined serum creatinine, urea, lipid profile and renal cortical mRNA expression for lipogenesis marker SREBP1, inflammatory macrophage marker iNOS and fibrosis markers; TGFβ and PDGFA genes; immunohistochemical (IHC) staining for CD68; inflammatory macrophage marker and ASMA; fibrosis marker, LC3 and SQSTM1/P62; autophagy markers and western blotting (WB) for caspase-3; and, as an apoptosis marker, LC3II/I and SQSTM1/P62 in addition to staining for H&E, PAS, Sirius red and histopathological scoring. Dasatinib attenuated renal cortical mRNA expression for SREBP1, iNOS, PDGFA and TGFβ and IHC staining for CD68, ASMA and SQSTM1/P62 and WB for caspase-3 and SQSTM1/P62, while elevating LC3 expression. Moreover, Dasatinib ameliorated ORC; glomerulosclerosis, glomerular expansion, tubular dilatation, vacuolation and casts; inflammatory cellular infiltration; and fibrosis. Dasatinib is a promising therapy for ORC by correcting autophagy impairment, attenuating lipogenesis, apoptosis and macrophage infiltration by inducing antifibrotic activity.

摘要

肥胖导致肾脏变化（ORC），其特征是肾自噬、脂生成、巨噬细胞浸润和凋亡受损。我们假设达沙替尼，一种酪氨酸激酶抑制剂，可能改善与肥胖相关的变化。我们用致肥胖饮食（OD）或标准基础饮食喂养小鼠。12 周后，小鼠接受载体或达沙替尼 4mg/kg/d 治疗，再持续 4 周。我们检测血清肌酐、尿素、脂质谱和肾皮质 mRNA 表达，以评估脂生成标志物 SREBP1、炎症性巨噬细胞标志物 iNOS 和纤维化标志物 TGFβ和 PDGFA 基因；免疫组织化学（IHC）染色用于 CD68；炎症性巨噬细胞标志物和 ASMA；纤维化标志物 LC3 和 SQSTM1/P62；自噬标志物和 WB 用于 caspase-3；以及作为凋亡标志物的 LC3II/I 和 SQSTM1/P62，此外还进行 H&E、PAS、天狼星红和组织病理学评分染色。达沙替尼可减弱肾皮质 SREBP1、iNOS、PDGFA 和 TGFβ 的 mRNA 表达以及 CD68、ASMA 和 SQSTM1/P62 的 IHC 染色和 WB 检测的 caspase-3 和 SQSTM1/P62，同时上调 LC3 的表达。此外，达沙替尼可改善 ORC；肾小球硬化、肾小球扩张、肾小管扩张、空泡化和管型；炎症细胞浸润；和纤维化。达沙替尼通过纠正自噬损伤、抑制脂生成、诱导抗纤维化活性来减少细胞凋亡和巨噬细胞浸润，为 ORC 提供了一种有前景的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/f19e06a2be1c/cells-11-00746-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/edee5094206e/cells-11-00746-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/60743c3f0cdc/cells-11-00746-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/73155bd3e4d5/cells-11-00746-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/b8bc9720dbc6/cells-11-00746-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/e100e00b39fe/cells-11-00746-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/f75481ac75b7/cells-11-00746-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/db07323dd90f/cells-11-00746-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/598ad5e0754c/cells-11-00746-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/a4b1dc48ffb0/cells-11-00746-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/f19e06a2be1c/cells-11-00746-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/edee5094206e/cells-11-00746-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/60743c3f0cdc/cells-11-00746-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/73155bd3e4d5/cells-11-00746-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/b8bc9720dbc6/cells-11-00746-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/e100e00b39fe/cells-11-00746-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/f75481ac75b7/cells-11-00746-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/db07323dd90f/cells-11-00746-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/598ad5e0754c/cells-11-00746-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/a4b1dc48ffb0/cells-11-00746-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4d7/8869974/f19e06a2be1c/cells-11-00746-g010.jpg

相似文献

1
Enhanced Autophagic Flux, Suppressed Apoptosis and Reduced Macrophage Infiltration by Dasatinib in Kidneys of Obese Mice.达沙替尼增强肥胖小鼠肾脏中的自噬通量，抑制细胞凋亡，减少巨噬细胞浸润。
Cells. 2022 Feb 21;11(4):746. doi: 10.3390/cells11040746.
2
Can Dasatinib Ameliorate the Hepatic changes, Induced by Long Term Western Diet, in Mice?达沙替尼能否改善长期西方饮食诱导的小鼠肝脏变化？
Ann Anat. 2021 Mar;234:151626. doi: 10.1016/j.aanat.2020.151626. Epub 2020 Nov 2.
3
m6A eraser FTO modulates autophagy by targeting SQSTM1/P62 in the prevention of canagliflozin against renal fibrosis.m6A 去甲基化酶 FTO 通过靶向 SQSTM1/P62 调节自噬，从而预防坎格列净引起的肾纤维化。
Front Immunol. 2023 Jan 4;13:1094556. doi: 10.3389/fimmu.2022.1094556. eCollection 2022.
4
Impaired autophagy flux is associated with neuronal cell death after traumatic brain injury.自噬通量受损与创伤性脑损伤后的神经元细胞死亡有关。
Autophagy. 2014;10(12):2208-22. doi: 10.4161/15548627.2014.981787.
5
Autophagic flux determines cell death and survival in response to Apo2L/TRAIL (dulanermin).自噬通量决定细胞对Apo2L/TRAIL（杜拉明）产生反应时的死亡与存活。
Mol Cancer. 2014 Mar 23;13:70. doi: 10.1186/1476-4598-13-70.
6
High-fat diet increases autophagic flux in pancreatic beta cells in vivo and ex vivo in mice.高脂肪饮食增加了体内和体外小鼠胰岛β细胞的自噬通量。
Diabetologia. 2015 Sep;58(9):2074-8. doi: 10.1007/s00125-015-3665-x. Epub 2015 Jun 14.
7
iNOS Interacts with Autophagy Receptor p62 and is Degraded by Autophagy in Macrophages.诱导型一氧化氮合酶（iNOS）与自噬受体 p62 相互作用，并在巨噬细胞中被自噬降解。
Cells. 2019 Oct 15;8(10):1255. doi: 10.3390/cells8101255.
8
Heat shock factor 1 confers resistance to Hsp90 inhibitors through p62/SQSTM1 expression and promotion of autophagic flux.热休克因子 1 通过 p62/SQSTM1 的表达和促进自噬通量赋予对 HSP90 抑制剂的抗性。
Biochem Pharmacol. 2014 Feb 1;87(3):445-55. doi: 10.1016/j.bcp.2013.11.014. Epub 2013 Nov 28.
9
The feedback loop of "EMMPRIN/NF-κB" worsens atherosclerotic plaque via suppressing autophagy in macrophage.“EMMPRIN/NF-κB”反馈环通过抑制巨噬细胞自噬作用加重动脉粥样硬化斑块。
J Mol Cell Cardiol. 2018 Jan;114:129-140. doi: 10.1016/j.yjmcc.2017.11.008. Epub 2017 Nov 14.
10
Depletion of the ubiquitin-binding adaptor molecule SQSTM1/p62 from macrophages harboring cftr ΔF508 mutation improves the delivery of Burkholderia cenocepacia to the autophagic machinery.从携带 cftr ΔF508 突变的巨噬细胞中耗尽泛素结合接头分子 SQSTM1/p62 可改善伯克霍尔德菌属到自噬机制的递呈。
J Biol Chem. 2013 Jan 18;288(3):2049-58. doi: 10.1074/jbc.M112.411728. Epub 2012 Nov 12.

引用本文的文献

1
Naringenin Mitigates Dasatinib-Induced Kidney Damage by Modulating Antioxidant Defense, Inflammation, and Apoptosis Pathways.柚皮素通过调节抗氧化防御、炎症和凋亡途径减轻达沙替尼诱导的肾损伤。
Int J Med Sci. 2025 Jan 1;22(1):110-120. doi: 10.7150/ijms.102088. eCollection 2025.
2
Cellular Senescence and Extracellular Vesicles in the Pathogenesis and Treatment of Obesity-A Narrative Review.细胞衰老与细胞外囊泡在肥胖发病机制及治疗中的作用：综述
Int J Mol Sci. 2024 Jul 20;25(14):7943. doi: 10.3390/ijms25147943.
3
Anti-proliferative activity of RIHMS-Qi-23 against MCF-7 breast cancer cell line is through inhibition of cell proliferation and senescence but not inhibition of targeted kinases.

本文引用的文献

1
Independent of Calorie Intake, Short-term Alternate-day Fasting Alleviates NASH, With Modulation of Markers of Lipogenesis, Autophagy, Apoptosis, and Inflammation in Rats.独立于热量摄入，短期隔日禁食可减轻 NASH，同时调节大鼠脂肪生成、自噬、凋亡和炎症的标志物。
J Histochem Cytochem. 2021 Sep;69(9):575-596. doi: 10.1369/00221554211041607. Epub 2021 Aug 27.
2
Senescence and senolytics in cardiovascular disease: Promise and potential pitfalls.衰老和衰老细胞清除在心血管疾病中的应用：前景与潜在风险。
Mech Ageing Dev. 2021 Sep;198:111540. doi: 10.1016/j.mad.2021.111540. Epub 2021 Jul 6.
3
Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy.
RIHMS-Qi-23 对 MCF-7 乳腺癌细胞系的抗增殖活性是通过抑制细胞增殖和衰老，而不是抑制靶向激酶。
BMC Cancer. 2023 Nov 2;23(1):1053. doi: 10.1186/s12885-023-11547-1.
4
Suppression of neuronal apoptosis and glial activation with modulation of Nrf2/HO-1 and NF-kB signaling by curcumin in streptozotocin-induced diabetic spinal cord central neuropathy.姜黄素通过调节Nrf2/HO-1和NF-κB信号通路抑制链脲佐菌素诱导的糖尿病脊髓中枢神经病变中的神经元凋亡和神经胶质细胞激活。
Front Neuroanat. 2023 Mar 9;17:1094301. doi: 10.3389/fnana.2023.1094301. eCollection 2023.
5
Methotrexate-Induced Alteration of Renal Aquaporins 1 and 2, Oxidative Stress and Tubular Apoptosis Can Be Attenuated by Omega-3 Fatty Acids Supplementation.甲氨蝶呤诱导的肾水通道蛋白 1 和 2 的改变、氧化应激和肾小管细胞凋亡可被ω-3 脂肪酸补充所抑制。
Int J Mol Sci. 2022 Oct 24;23(21):12794. doi: 10.3390/ijms232112794.
进行性细胞衰老介导缺血性肾病中的肾功能障碍。
J Am Soc Nephrol. 2021 Aug;32(8):1987-2004. doi: 10.1681/ASN.2020091373. Epub 2021 Jun 16.
4
Eicosapentaenoic and docosahexaenoic acids attenuate methotrexate-induced apoptosis and suppression of splenic T, B-Lymphocytes and macrophages with modulation of expression of CD3, CD20 and CD68.二十碳五烯酸和二十二碳六烯酸可通过调节 CD3、CD20 和 CD68 的表达来减轻甲氨蝶呤诱导的脾 T、B 淋巴细胞和巨噬细胞凋亡和抑制作用。
Tissue Cell. 2021 Oct;72:101533. doi: 10.1016/j.tice.2021.101533. Epub 2021 Mar 23.
5
Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines.低剂量达沙替尼改善多发性黑子综合征肥厚型心肌病。
Cardiovasc Drugs Ther. 2022 Aug;36(4):589-604. doi: 10.1007/s10557-021-07169-z. Epub 2021 Mar 10.
6
Dasatinib mitigates renal fibrosis in a rat model of UUO via inhibition of Src/STAT-3/NF-κB signaling.达沙替尼通过抑制Src/STAT-3/NF-κB 信号通路减轻 UUO 大鼠模型的肾纤维化。
Environ Toxicol Pharmacol. 2021 May;84:103625. doi: 10.1016/j.etap.2021.103625. Epub 2021 Feb 19.
7
Senolytic therapy ameliorates renal fibrosis postacute kidney injury by alleviating renal senescence.衰老细胞清除疗法通过减轻肾脏衰老改善急性肾损伤后的肾纤维化。
FASEB J. 2021 Jan;35(1):e21229. doi: 10.1096/fj.202001855RR.
8
Can Dasatinib Ameliorate the Hepatic changes, Induced by Long Term Western Diet, in Mice?达沙替尼能否改善长期西方饮食诱导的小鼠肝脏变化？
Ann Anat. 2021 Mar;234:151626. doi: 10.1016/j.aanat.2020.151626. Epub 2020 Nov 2.
9
Obesity-Related Glomerulopathy: A Latent Change in Obesity Requiring More Attention.肥胖相关性肾小球病：肥胖中的一种潜在变化，需要更多关注。
Kidney Blood Press Res. 2020;45(4):510-522. doi: 10.1159/000507784. Epub 2020 Jun 4.
10
Comparison of autophagy inducibility in various tyrosine kinase inhibitors and their enhanced cytotoxicity via inhibition of autophagy in cancer cells in combined treatment with azithromycin.各种酪氨酸激酶抑制剂的自噬诱导能力比较以及它们在与阿奇霉素联合治疗时通过抑制癌细胞自噬增强细胞毒性的研究。
Biochem Biophys Rep. 2020 Mar 17;22:100750. doi: 10.1016/j.bbrep.2020.100750. eCollection 2020 Jul.