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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

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【作者】 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

【Author】 WANG Song;GUO Yingze;LI Tianshu;SONG Jinping;LIU Keyuan;ZHOU Wei;ZHAO Lijing;JIANG Tiechao;GUO Lirong;Department of Rehabilitation,School of Nursing,Jilin University;Department of Pathophysiology,School of Basic Medical Sciences,Jilin University;Department of Clinical Laboratory,First Hospital,Jilin University;Department of Cardiology,China-Japan Union Hospital,Jilin University;

【通讯作者】 姜铁超;郭丽荣;

【机构】 吉林大学护理学院康复治疗学系吉林大学基础医学院病理生理学系山东协和学院吉林大学第一医院检验科吉林大学中日联谊医院心内科

【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(AngⅡ)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400bp处有1条碱基片段,杂合子小鼠在250和400bp处各有1条碱基片段,UT-B-/-小鼠在250bp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AngⅡ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AngⅡ和脑脊液钠离子水平有关。

【Abstract】 Objective:To investigate the effect of high salt diet on the arterial blood pressure in the ureatransporter 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 4weeks.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 angiotensinⅡ(AngⅡ)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 a400bp base fragment in the UT-B+/+mice,250and 400bp base fragments in the UT-B+/-mice,and 250bp 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 AngⅡlevel 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 AngⅡlevel and the Na+level in cerebrospinal fluid in the mice.

【基金】 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)
  • 【文献出处】 吉林大学学报(医学版) ,Journal of Jilin University(Medicine Edition) , 编辑部邮箱 ,2019年05期
  • 【分类号】R544.1;R-332
  • 【被引频次】4
  • 【下载频次】249
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