Infusion of Valproic Acid Into the Renal Medulla Activates Stem Cell Population and Attenuates Salt-Sensitive Hypertension in Dahl S Rats.
Infusion of Valproic Acid Into the Renal Medulla Activates Stem Cell Population and Attenuates Salt-Sensitive Hypertension in Dahl S Rats.
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DOI：
10.1159/000478955
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Li N
中科院分区：
文献类型：
--
作者：
Wang Z;Zhu Q;Wang W;Yi F;Li PL;Boini KM;Li N
我们之前的研究已经在达尔盐敏感(S)大鼠的肾髓质中发现了干细胞缺乏。本研究确定输注丙戊酸（VA）是否能减轻达尔S大鼠的盐敏感性高血压。丙戊酸是一种已知能刺激干细胞功能的药物。未切除肾的Dahl S大鼠在肾髓质内注入载药或VA (50mg/kg/d)，分别饲喂低盐（LS）或高盐饮食（HS）。采用免疫组织化学、Real-time RT-PCR和Western blot分析干细胞标记物和数量。测定钠排泄量和血压。VA显著提高了干细胞生态位因子FGF2和干细胞标志物CD133的mRNA和蛋白水平。va处理大鼠肾髓质中CD133+细胞数量显著增加。同时，高盐诱导的促炎因子白介素-1β和白介素-6 mRNA水平升高被va处理大鼠阻断。功能上，va处理大鼠血压升高和急性钠负荷时钠排泄明显增强，钠潴留减弱，高盐引起的血压升高降低。VA激活干细胞功能可抑制促炎因子的激活，减轻Dahl S大鼠盐敏感性高血压。
Our previous study has detected a stem cell deficiency in the renal medulla in Dahl salt-sensitive (S) rats. This study determined whether infusion of valproic acid (VA), an agent known to stimulate the stem cell function, attenuated salt-sensitive hypertension in Dahl S rats. Uninephrectomized Dahl S rats were infused with vehicle or VA (50mg/kg/d) into the renal medulla and fed with a low (LS) or high salt diet (HS). Stem cell marker and number were analyzed by immunohistochemistry, Real-time RT-PCR and Western blot. Sodium excretion and blood pressure were measured. VA significantly increased the mRNA and protein levels of FGF2, a stem cell niche factor, and CD133, a stem cell marker. The number of CD133+ cells was significantly increased in the renal medulla in VA-treated rats. Meanwhile, high salt-induced increases in the mRNA level of proinflammatory factors interleukin-1β and interleukin-6 were blocked in VA-treated rats. Functionally, sodium excretion in response to the blood pressure increase and acute sodium loading was significantly enhanced, sodium retention attenuated, high salt-induced increase of blood pressure reduced in VA-treated rats. Activation of stem cell function by VA inhibits the activation of proinflammatory factors and attenuates salt-sensitive hypertension in Dahl S rats.
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DOI：
10.1152/ajpregu.00567.2002
发表时间：
2003-03-01
影响因子：
2.8
作者：
Cowley, AW
通讯作者：
Cowley, AW
DOI：
10.1152/ajprenal.00288.2014
发表时间：
2014-10-15
影响因子：
4.2
作者：
Mirabito, Katrina M.;Hilliard, Lucinda M.;Denton, Kate M.
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Denton, Kate M.
影响因子：
4.7
作者：
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通讯作者：
Altar, CA
DOI：
10.1111/j.1365-201x.2004.01321.x
发表时间：
2004-08-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Bergström, G;Evans, RG
通讯作者：
Evans, RG
影响因子：
4.4
作者：
Lagali, Neil;Eden, Ulla;Fagerholm, Per
通讯作者：
Fagerholm, Per