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Circulation：钠糖共转运体抑制剂的肾保护作用机制

2019-08-06 MedSci MedSci原创

钠糖共转运体依帕列净腺苷入球小动脉
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钠-葡萄糖共转运体2抑制剂可减少肾脏的超滤过，从而防止糖尿病肾病的进展，进而降低心血管疾病的风险，包括心力衰竭。但钠-葡萄糖共转运体2抑制剂调节肾功能反应的机制尚未完全明确。现研究人员用依帕列净来研究钠-葡萄糖钠共转运体2抑制剂对肾脏的保护作用，重点研究肾小球血流动力学效应和球管反馈。用依帕列净和胰岛素来治疗野生型和自发糖尿病的Ins2+/Akita小鼠，4周，检测肾单位肾小球滤过率。用神经元NO

钠-葡萄糖共转运体2抑制剂可减少肾脏的超滤过，从而防止糖尿病肾病的进展，进而降低心血管疾病的风险，包括心力衰竭。但钠-葡萄糖共转运体2抑制剂调节肾功能反应的机制尚未完全明确。现研究人员用依帕列净来研究钠-葡萄糖钠共转运体2抑制剂对肾脏的保护作用，重点研究肾小球血流动力学效应和球管反馈。

用依帕列净和胰岛素来治疗野生型和自发糖尿病的Ins2+/Akita小鼠，4周，检测肾单位肾小球滤过率。用神经元NO合酶抑制剂（7-硝基吲唑）、环氧化酶2抑制剂或A1腺苷受体拮抗剂来阐明球管反馈信号和肾单位肾小球滤过率调控。

检测尿中的腺嘌呤、NO代谢产物和前列腺素E2。Ins2+/Akita组的肾单位肾小球滤过率高于对照组（15.8±6.8 nL/min vs 4.9±1.3nL/min），而用依帕列净处理的Ins2+/Akita组的肾单位肾小球滤过率则降至8.0±3.3 nL/min。此外，研究人员还发现Ins2+/Akita组的入球小动脉扩张，肾小球白蛋白通透性增高。依帕列净可改善上述改变。Ins2+/Akita依帕列净组的尿腺苷量高于Ins2+/Akita组（11.2±3.0nmol/d vs 3.4±1.4nmol/d，p<0.05），但NO合酶和环氧化酶2无差别。是A1腺苷受体拮抗剂阻断了依帕列净对肾功能的作用，而NO合酶和环氧化酶2抑制剂无此效应。依帕列净可通过收缩入球小动脉增加尿腺苷分泌、减少超滤，该作用可被A1腺苷受体阻断。

在钠-葡萄糖共转运体2抑制剂的作用下，腺苷/A1腺苷受体通路通过球管反馈机制，调节肾单位肾小球滤过率。

原始出处：

Kengo Kidokoro，et al.Evaluation of Glomerular Hemodynamic Function by Empagliflozin in Diabetic Mice Using In Vivo Imaging.https：//doi.org/10.1161/CIRCULATIONAHA.118.037418Circulation. 2019；140：303–315

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    2019-08-08 yzh409

    #转运#

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    2020-03-05 jklm09

    #抑制剂#

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    2019-09-14 liujie6118

    学习新知识

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    2019-08-07 photoman

    #保护作用#

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    2019-08-06 1e1c07bdm01(暂无匿称)

    好

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