Wang Zhengchao, Zhu Qing, Wang Weili, Yi Fan, Li Pin-Lan, Boini Krishna M, Li Ningjun
Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, China.
Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia, USA.
Cell Physiol Biochem. 2017;42(3):1264-1273. doi: 10.1159/000478955. Epub 2017 Jul 11.
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.
我们之前的研究已检测到达尔盐敏感（S）大鼠肾髓质存在干细胞缺陷。本研究确定了输注丙戊酸（VA），一种已知可刺激干细胞功能的药物，是否能减轻达尔S大鼠的盐敏感性高血压。
对单侧肾切除的达尔S大鼠肾髓质输注溶媒或VA（50mg/kg/天），并给予低（LS）盐或高盐饮食（HS）。通过免疫组织化学、实时逆转录聚合酶链反应和蛋白质印迹分析干细胞标志物和数量。测量钠排泄和血压。
VA显著增加了干细胞龛因子FGF2和干细胞标志物CD133的mRNA和蛋白质水平。在接受VA治疗的大鼠肾髓质中，CD133+细胞数量显著增加。同时，在接受VA治疗的大鼠中，高盐诱导的促炎因子白细胞介素-1β和白细胞介素-6 mRNA水平的升高被阻断。在功能上，接受VA治疗的大鼠对血压升高和急性钠负荷的钠排泄显著增强，钠潴留减轻，高盐诱导的血压升高降低。
VA激活干细胞功能可抑制促炎因子的激活，并减轻达尔S大鼠的盐敏感性高血压。
