高盐饮食对尿素通道蛋白B基因缺失小鼠动脉血压的影响及其机制

doi:10.13481/j.1671-587x.20190514

吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (05): 1052-1057.doi: 10.13481/j.1671-587x.20190514

• 基础研究 • 上一篇

高盐饮食对尿素通道蛋白B基因缺失小鼠动脉血压的影响及其机制

王松^1,2, 郭瀛泽, 李天舒², 宋金萍², 刘科苑², 周伟³, 赵丽晶¹, 姜铁超⁴, 郭丽荣^1,2

1. 吉林大学护理学院康复治疗学系, 吉林长春 130021;
2. 吉林大学基础医学院病理生理学系, 吉林长春 130021;
3. 吉林大学第一医院检验科, 吉林长春 130021;
4. 吉林大学中日联谊医院心内科, 吉林长春 130033

收稿日期:2018-01-22 发布日期:2019-10-08
通讯作者: 郭丽荣,副教授,硕士研究生导师(Tel:0431-85622010,E-mail:guolr@jlu.edu.cn);姜铁超,副教授,硕士研究生导师(Tel:0431-84995259,E-mail:jiangtc@jlu.edu.cn) E-mail:guolr@jlu.edu.cn;jiangtc@jlu.edu.cn
作者简介:王松(1992-),女,山东省阳谷县人,医学硕士,主要从事盐敏感性高血压方面的研究。
基金资助:
吉林省科技厅国际合作项目资助课题（20140414012GH）；吉林省教育厅"十三五"科学技术项目资助课题（JJKH20190103KJ，吉教科合字[2015]第498号）；吉林大学白求恩B计划项目资助课题（2015221）

Effect of high salt diet on arterial blood pressure in urea transporter B gene depletion mice and its mechanism

WANG Song^1,2, GUO Yingze, LI Tianshu², SONG Jinping², LIU Keyuan², ZHOU Wei³, ZHAO Lijing¹, JIANG Tiechao⁴, GUO Lirong^1,2

1. Department of Rehabilitation, School of Nursing, Jilin University, Changchun 130021, China;
2. Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China;
3. Department of Clinical Laboratory, First Hospital, Jilin University, Changchun 130021, China;
4. Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun 130033, China

Received:2018-01-22 Published:2019-10-08

摘要/Abstract

摘要： 目的：探讨高盐饮食对尿素通道蛋白B基因（UT-B）缺失（UT-B^-/-）小鼠动脉血压的影响，阐明UT-B^-/-导致小鼠动脉血压改变的可能机制。方法：杂合子小鼠交配获得遗传背景相同野生型（UT-B^+/+）小鼠和UT-B^-/-小鼠；选取4周龄雄性UT-B^+/+小鼠和UT-B^-/-小鼠，分别给予4周普通饮食（0.3% NaCl）或高盐饮食（8.0% NaCl），分为UT-B^+/+小鼠+普通饮食组（UT-B^+/++N）、UT-B^-/-小鼠+普通饮食组（UT-B^-/-+N）、UT-B^+/+小鼠+高盐饮食组（UT-B^+/++H）和UT-B^-/-小鼠+高盐饮食组（UT-B^-/-+H），共4组。监测各组小鼠饮水量和平均动脉压的变化，采用RT-PCR法、Western blotting法和免疫组织化学法检测脑组织脉络丛（CP） UT-B mRNA和蛋白表达水平和定位，ELISA法检测各组小鼠血清血管紧张素Ⅱ（Ang Ⅱ）水平和脑脊液中钠离子水平。结果： PCR法检测鼠尾基因组DNA，UT-B^+/+小鼠在400 bp处有1条碱基片段，杂合子小鼠在250和400 bp处各有1条碱基片段，UT-B^-/-小鼠在250 bp处有1条碱基片段。与普通饮食组比较，高盐饮食组小鼠饮水量明显增加（P<0.01）；与UT-B^-/-小鼠+普通饮食组和UT-B^+/+小鼠＋高盐饮食组比较，UT-B^-/-小鼠＋高盐饮食组小鼠平均动脉压明显升高（P<0.01）；UT-B mRNA和蛋白表达于UT-B^+/+小鼠脑组织CP上皮细胞。与UT-B^-/-小鼠＋普通饮食组和UT-B^+/+小鼠＋高盐饮食组比较，UT-B^-/-小鼠＋高盐饮食组小鼠血清Ang Ⅱ水平明显升高（P<0.01），脑脊液中钠离子水平明显升高（P<0.05）。结论：高盐饮食可导致UT-B^-/-小鼠平均动脉压明显升高，其机制与升高小鼠血清Ang Ⅱ和脑脊液钠离子水平有关。

关键词: 高盐饮食, 尿素通道蛋白B, 平均动脉压, 脑脊液, 钠离子

Abstract: Objective:To investigate the effect of high salt diet on the arterial blood pressure in the urea transporter B(UT-B) gene depletion (UT-B ^-/-) mice, and to clarify the possible mechanism of the UT-B^-/- leading to the changes in the arterial blood pressure of the mice. Methods:The heterozygous (UT-B^+/-) mice were mated to obtain the wild-type (UT-B^+/+) and UT-B^-/- mice with the same genetic background. The 4-week-old male UT-B^+/+ and UT-B^-/- mice were selected and fed on normal diet (0.3% NaCl) or high salt diet (8.0% NaCl) for 4 weeks. The mice were divided into UT-B^+/+ mice+normal diet (UT-B^+/++N) group,UT-B^-/- mice +normal diet (UT-B^-/-+N) group,UT-B^+/+ mice+high salt diet(UT-B^+/++H) group,and UT-B^-/- mice+high salt diet(UT-B^-/-+H) group. The changes in water intakes and mean arterial pressures of the mice in various groups were monitored; RT-PCR, Western blotting and immunohistochemistry were used to detect the expression levels and location of UT-B mRNA and protein in choroid plexus(CP) of the brain tissue of the mice. The levels of serum angiotensin Ⅱ (Ang Ⅱ) and the Na⁺ levels in cerebrospinal fluid of the mice in various groups were determined by ELISA. Results:The PCR results of genomic DNA of mouse tail showed that there was a 400 bp base fragment in the UT-B^+/+ mice, 250 and 400 bp base fragments in the UT-B^+/- mice, and 250 bp base fragment in the UT-B^-/- mice. Compared with normal salt diet group, the water intake of the mice in high salt diet was significantly increased (P<0.01); compared with UT-B^-/-+N group and UT-B^+/++H group,the mean arterial pressure of the mice in UT-B^-/-+H group was significantly increased(P<0.01).The UT-B mRNA and protein expressed in the epithelial cells of CP in the UT-B^+/+ mice. Compared with UT-B^-/-+N group and UT-B^+/+ mice+H group, the Ang Ⅱ level in serum of the mice in UT-B^-/- mice+H group was significantly increased (P<0.01); the Na⁺ level in cerebrospinal fluid of the mice was significantly increased (P<0.05). Conclusion:High salt diet can cause a significant increase in the mean arterial pressure in the UT-B^-/- mice, and its mechanism is related to increasing the serum Ang Ⅱ level and the Na⁺ level in cerebrospinal fluid in the mice.

Key words: high salt diet, urea transporter B, mean arterial pressure, cerebrospinal fluid, sodium ion

中图分类号:

王松, 郭瀛泽, 李天舒, 宋金萍, 刘科苑, 周伟, 赵丽晶, 姜铁超, 郭丽荣. 高盐饮食对尿素通道蛋白B基因缺失小鼠动脉血压的影响及其机制[J]. 吉林大学学报(医学版), 2019, 45(05): 1052-1057.

WANG Song, GUO Yingze, LI Tianshu, SONG Jinping, LIU Keyuan, ZHOU Wei, ZHAO Lijing, JIANG Tiechao, GUO Lirong. Effect of high salt diet on arterial blood pressure in urea transporter B gene depletion mice and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1052-1057.

参考文献

[1] MARQUES F Z,MACKAY C R,KAYE D M. Beyond gut feelings:how the gut microbiota regulates blood pressure[J]. Nature Rev Cardiol, 2018, 15(1):20-32.
[2] NOVELLO M F, RPSA M L, FERREIRA R T, et al. Compliance with the Prescription of antihypertensive medications and blood Pressure control in Primary Care[J]. Arq Bras Cardiol, 2017, 108(2):135-142.
[3] FRANCESCO T, MIRIAM Z. The role of the kidney in salt-sensitive hypertension[J]. Clin Exp Nephrol, 2012, 16(1):68-72.
[4] LU J P, LU Y, WANG X C, et al. Prevalence, awareness, treatment, and control of hypertension in China-data from 1.7 million adults in a population-based screening study (China PEACE Million Persons Project)[J]. Lancet, 2017, 390(10112):2549-2558.
[5] 陈伟伟, 高润霖, 胡盛寿.《中国心血管病报告2017》概要[J]. 中国循环杂志, 2017, 32(6):521-530.
[6] 罗怡, 陈明. 盐敏感性高血压研究进展[J]. 心血管病学进展, 2013, 34(5):644-647.
[7] GUO L R, MENG J, XUAN C L, et al. High salt-diet reduces SLC14A1 gene expression in the choroid plexus of Dahl salt sensitive rats[J]. Biochem Biophys Res Commun, 2015, 461(2):254-259.
[8] 钟丹丹, 杨宝学. 尿素通道蛋白B的转运特性[J]. 生理学研究, 2014, 2(1):1-4.
[9] LIU L Q, SUN Y X, ZHAO Y X, et al. Urea transport B gene induces melanoma B16 cell death via activation of p53 and mitochondrial apoptosis[J]. Cancer Sci, 2018, 109(12):3762-3773.
[10] LI X C, CHEN G P, YANG B X. Urea transporter physiology studied in knockout mice[J]. Front Physiol, 2012, 3:217.
[11] GENG X Q, LEI T L, ZHOU H, et al. The knockout of urea transporter-B improves the hemorheological properties of erythrocyte[J]. Clin Hemorheol Microcirc, 2017, 65(3):249-257.
[12] KLEIN J D. Expression of urea transporters and their regulation[J]. Subcell Biochem, 2014, 73(1):79-107.
[13] 姜涛, 杨宝学. 尿素通道蛋白的组织分布和生理功能[J]. 神经药理学报, 2015, 5(5):40-48.
[14] KOTCHEN T A, COWLEY A W,FROHLICH E D. Salt in health and disease-A delicate balance[J]. N Engl J Med, 2013, 368(13):1229-1237.
[15] BLAUSTEIN M P, LEENEN F H H, CHEN L, et al. How NaCl raise blood pressure:a new paradigm for the pathogenesis of salt-dependent hypertension[J]. Am J Physiol Heart Circ Physiol, 2012, 302(5):H1031-H1049.
[16] JIANG E S, CHAPP A D, FAN Y Y, et al. Expression of proinflammatory cytokines is upregulated in the hypothalamic paraventricular nucleus of Dahl salt-sensitive hypertensive rats[J]. Front Physiol, 2018, 9:104.
[17] NAKANO M, HIROOKA Y, MATSUKAWA R, et al. Mineralocorticoid-receptors/epithelial Na⁺ channels in the choroid plexus are involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats[J]. Hypertens Res, 2013, 36(3):277-284.
[18] KIBATHI L W, BAE S, PENZAK S R, et al. Potential influence of centrally acting herbal drugs on transporters at the blood-cerebrospinal fluid barrier and blood-brain barrier[J]. Eur J Drug Metab Pharmacokinet, 2018, 43(6):619-635.
[19] TUMANI H, HUSS A, BACHHUBER F. The cerebrospinal fluid and barriers-anatomic and physiologic considerations[J]. Handb Clin Neurol, 2017, 146(1):21-32.
[20] SANDS J M, BLOUNT M A. Genes and proteins of urea transporters[J]. Subcell Biochem, 2014, 73:45-63.
[21] ESTEVA-FONT C, ANDERSON M O, VERKMAN A S. Urea transporter proteins as targets for small-molecule diuretics[J]. Nat Rev Nephrol, 2015, 11(2):113-123.
[22] SCHWEDA F. Salt feedback on the renin-angiotensin-aldosterone system[J]. Pflugers Arch, 2015, 467(3):565-576. *山东协和学院护理学专业2015级

高盐饮食对尿素通道蛋白B基因缺失小鼠动脉血压的影响及其机制

Effect of high salt diet on arterial blood pressure in urea transporter B gene depletion mice and its mechanism

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

Metrics

本文评价

推荐阅读 0

[1]	历春, 付天悦, 杨宝学, 盖晓东. 尿素通道蛋白B在人膀胱癌组织中的表达及其临床意义[J]. 吉林大学学报(医学版), 2017, 43(04): 705-708.
[2]	邓旺，赵燕，何婧，王导新. 胰岛素通过PI3K信号通路对肺泡上皮钠通道β亚基表达的调控[J]. 吉林大学学报(医学版), 2014, 40(02): 233-237.
[3]	赵丽晶，路明，韩雪，张睿，李若文，赵雪俭，杨宝学，郭丽荣. UT-B基因敲除小鼠睾丸间质细胞睾酮分泌水平变化及其对性成熟的影响[J]. 吉林大学学报(医学版), 2013, 39(3): 448-452.
[4]	董迎春，邵云，苏荣祥，吴蔚媚，李刚. 光棒引导经鼻气管内插管在困难气道患者气管插管中的应用及其效果评价[J]. 吉林大学学报(医学版), 2013, 39(3): 592-596.
[5]	李海波，张波，常桂芬，王慧，梁建民，卢洪华. 小儿化脓性脑膜炎和病毒性脑膜炎患者脑脊液中IGF-Ⅱ和IGFBP-3的检测及临床意义[J]. J4, 2009, 35(1): 167-169.