Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption.
Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption.
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DOI：
10.26599/1671-5411.2023.07.001
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发表时间：
2023-07
期刊：
影响因子：
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通讯作者：
Qiong-yu Zhang;Yangming Guo;Xiaoliang Jiang;Xing Liu;Shu-guang Zhao;Xianliang Zhou;Zhiwei Yang
中科院分区：
文献类型：
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作者：
Qiong-yu Zhang;Yangming Guo;Xiaoliang Jiang;Xing Liu;Shu-guang Zhao;Xianliang Zhou;Zhiwei Yang
目的探讨CCKBRf 1/f1 villin-Cre小鼠作为盐敏感性高血压（SSH）小鼠模型的价值。方法：第一部分，将2月龄CCKBRfl/fl villin-Cre小鼠（CKO）和对照组CCKBRfl/fl小鼠（WT）分别给予正常饲料（0.4%NaCl）和高盐饲料（4%NaCl）喂养6周。在补救研究中，对喂食高盐饮食的CKO小鼠注射氢氯噻嗪或生理盐水一周。检测血压、生化指标及小肠钠转运蛋白（NHE 3、NKCC 1、eNaC）的表达。观察肾脏组织病理学变化及脏器损伤标志物MMP 2/MMP 9的变化，并采用在体小肠灌流法检测十二指肠钠吸收的变化。结果CCKBRfl/fl villin-Cre小鼠高盐摄入后血压升高，十二指肠钠吸收和尿钠排泄增加，肾功能损害。CKO-HS小鼠肠组织中NHE 3、NKCC 1和eNaC的蛋白表达也显著增加。在CCKBRfl/fl villin-Cre小鼠中，氢氯噻嗪治疗显著减弱了高盐吸收引起的血压升高，但未观察到显著的组织病理学变化。结论肠道Cckbr缺陷对CCKBRfl/fl villin-Cre小鼠SSH的发生和利尿降压作用具有重要作用。高盐摄入的CCKBRfl/fl villin-Cre小鼠可作为钠超载诱导盐敏感性高血压的稳定模型。
OBJECTIVES To investigate the value of CCKBRfl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH). METHODS In the first part, 2-month-old CCKBRfl/fl villin-Cre mice (CKO) and control CCKBRfl/fl mice (WT) were fed with normal diet (0.4% NaCl) or high salt diet (4% NaCl), separately for 6 weeks. In the rescue study, one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet. The blood pressure, biochemical indexes, and the expression of small intestinal sodium transporters (NHE3, NKCC1, eNaC) was detected. The organ injury markers (MMP2/MMP9) and the histopathological changes of kidneys were observed, whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo. RESULTS The CCKBRfl/fl villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBRfl/fl villin-Cre mice, but no significant histopathological changes were observed. CONCLUSIONS These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic antihypertension effect in CCKBRfl/fl villin-Cre mice. The CCKBRfl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.