Renovascular hypertension: Effects of mesenchymal stem cells in the contralateral hypertensive kidney in rats
Renovascular hypertension: Effects of mesenchymal stem cells in the contralateral hypertensive kidney in rats
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DOI：
10.3109/10641963.2016.1174253
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发表时间：
2016-01-01
影响因子：
12.3
通讯作者：
Boim, Mirian Aparecida
中科院分区：
文献类型：
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作者：
de Oliveira-Sales, Elizabeth Barbosa;Varela, Vanessa Araujo;Boim, Mirian Aparecida
间充质干细胞（MSC）诱导新血管形成，并改善肾血管性高血压的双肾一夹（2K-1C）模型中狭窄肾的肾形态。本研究评价了MSC在对侧高血压肾中的作用。左肾动脉阻断3周后，将MSC注入2K-1C大鼠尾静脉。分析双肾的肾功能和形态学。标记的MSC被发现在狭窄和对侧肾脏。高血压2K-1C动物的血管紧张素II（Ang II）和肾素的循环水平增加。MSC阻止了血压的进行性升高，并降低了循环血管紧张素II和肾素水平。狭窄肾显示肾血浆流量（RPF）和肾小球滤过率（GFR）降低，而对侧肾尽管RPF不变，但GFR有降低的趋势（p > 0.5）。MSC治疗引起GFR的改善，而对狭窄肾脏中的RPF没有影响。侧肾显示利尿和尿钠排泄增加，在MSC处理的动物中甚至更高，表明细胞处理改善了对侧肾排泄钠的能力。侧肾表达较高水平的炎性细胞因子（IL-6，TNF-α）和纤维化的迹象，这是减弱MSC治疗。MSC治疗改善了狭窄的肾功能，并且对对侧高血压肾也是有益的，因为它改善了形态并保留了其排钠能力。
Mesenchymal stem cells (MSC) induced neovascularization and improved renal morphology of the stenotic kidney in 2 kidneys-1 clip (2K-1C) model of renovascular hypertension. The present study evaluated the effects of MSC in the contralateral hypertensive kidney. Three weeks after left renal artery occlusion, MSC were injected into the tail vein of the 2K-1C rats. Renal function and morphology were analyzed in both kidneys. Labeled MSC were found in stenotic and contralateral kidneys. Hypertensive 2K-1C animals presented increased circulating levels of Angiotensin II (Ang II) and renin. MSC prevented the progressive increase of blood pressure and reduced circulating Ang II and renin levels. Stenotic kidney showed reduced renal plasma flow (RPF) and glomerular filtration rate (GFR), whereas the contralateral kidney had a tendency (p > 0.5) of reduction in GFR in spite of unchanged RPF. MSC treatment caused an improvement in GFR with no effect of on RPF in the stenotic kidney. Contralateral kidney showed increased diuresis and natriuresis that were even higher in MSC-treated animals, indicating that cell treatment improved the capacity of the contralateral kidney to excrete sodium. Contralateral kidney expressed higher levels of inflammatory cytokines (IL-6, TNF-) and signs of fibrosis, which were attenuated by MSC treatment. MSC treatment improved the stenotic kidney function, and it was also beneficial to the contralateral hypertensive kidney because it improved the morphology and preserved its capacity to excrete sodium.