北京大学学报(医学版) ›› 2015, Vol. 47 ›› Issue (1): 149-154.

• 论著 • 上一篇    下一篇

高盐饮食上调肾局部肾素-血管紧张素系统参与大鼠高血压肾损害的发生

吴海燕,梁耀先,郑亦沐,白琼,庄震,阿拉塔,郑丹侠,王悦△   

  1. (北京大学第三医院肾内科,北京100191)
  • 出版日期:2015-02-18 发布日期:2015-02-18

Up-regulation of intrarenal renin-agiotensin system contributes to renal damage in high-salt induced hypertension rats

WU Hai-yan, LIANG Yao-xian, ZHENG Yi-mu, BAI Qiong, ZHUANG Zhen, A La-ta, ZHENG Dan-xia, WANG Yue△   

  1. (Department of Nephrology, Peking University Third Hospital, Beijing 100191, China)
  • Online:2015-02-18 Published:2015-02-18

摘要: 目的:探讨肾脏局部肾素-血管紧张素系统(renin-agiotensin system,RAS)在高盐诱发大鼠高血压及其肾损害发病机制中的作用。方法:8周龄雄性Wistar大鼠随机分为3组:对照组(NS,n=9),普通饲料喂养;高盐组(HS,n=9),含8%(质量分数)NaCl的高盐饲料喂养;高盐饮食+氯沙坦组(HS+L,n=9),高盐饲料喂养同时每日给予氯沙坦20 mg/kg灌胃。实验共6周,期间每2周监测血压和24 h尿蛋白,6周后处死大鼠,放射免疫法测定血浆、肾脏匀浆以及尿液的肾素活性、血管紧张素Ⅱ水平,Real-time PCR、免疫组织化学染色分别检测肾脏血管紧张素原(angiotensinogen,AGT)mRNA、蛋白表达水平,ELISA测定血、肾皮质匀浆液以及尿AGT水平。结果:与NS组相比,HS组大鼠第2周始血压显著升高[(156±2) mmHg vs. (133±3) mmHg (1 mmHg=0.133 kPa), P<0.05)],第6周时尿蛋白显著增加[(14.07±2.84) mg/24 h vs. (7.62±3.02) mg/24 h, P<0.05];HS+L组与HS组大鼠血压差异无统计学意义(P>0.05),但第6周时HS+L组尿蛋白比HS组显著降低[(9.69±2.73) mg/24 h vs. (14.07±2.84) mg/24 h, P<0.01]。与NS组相比,HS组血浆肾素活性、AGT和血管紧张素Ⅱ(angiotensin Ⅱ,ANGⅡ)水平无显著变化(P>0.05),肾皮质肾素活性、AGT 和ANGⅡ水平均显著升高(P<0.05),尿AGT和ANGⅡ排泄率均显著升高(P<0.05);与HS组相比,HS+L组大鼠血浆肾素活性、AGT和ANGⅡ水平均显著升高(P<0.05),肾皮质肾素活性、ANGⅡ和AGT水平均显著降低(P<0.05),尿AGT和ANGⅡ排泄率均显著降低(P<0.01),尿AGT排泄率与肾皮质AGT水平呈显著正相关(P<0.05)。结论:高盐可能通过上调肾脏局部RAS的表达参与大鼠的肾损害,尿AGT排泄率可能反映肾脏局部RAS激活的程度。

关键词: 氯化钠, 膳食, 肾素-血管紧张素系统, 高血压, 蛋白尿, 血管紧张素原

Abstract: Objective: To test the hypothesis that in a high-salt induced hypertension in normal rats, whether the changes of intrarenal renin-agiotensin system (RAS) play a critical role in renal damage and could be reflected by urinary angiotensinogen (AGT). Methods: In the study, 27 normotensive male Wistar-Kyoto rats were divided into control group [0.3% (mass faction) NaCl in chow, n=9, NS], high-salt diet group [8% (mass faction) NaCl in chow, n=9, HS] and high-salt diet with Losartan group [8% (mass faction) NaCl in chow and 20 mg/(kg·d) Losartan in gavages, n=9, HS+L)], and were fed for six weeks. The blood pressure was monitored and urine samples were collected every 2 weeks. AGTs in plasma, kidney and urine were measured by ELISA kits. The renal cortex expression of mRNA and protein of AGT were measured by Real-time PCR and immunohistochemistry (IHC). The renin activity and ANGⅡ were measured by radioimmunoassay (RIA) kits. Results: Compared with NS, the systolic blood pressure (SBP) [(156±2) mmHg vs. (133±3) mmHg, P<0.05] increased significantly at the end of the 2nd week, and the urinary protein [(14.07±2.84) mg/24 h vs. (7.62±3.02) mg/24 h, P<0.05] increased significantly at the end of the 6th week in HS. Compared with HS, there was no significant difference in SBP (P>0.05) but the proteinuria [(9.69±2.73) mg/24 h vs. (14.07±2.84) mg/24 h, P<0.01] decreased significantly in HS+L. Compared with NS, there was no significant difference in the plasma renin activity, angiotensinogen and ANGⅡ level in HS (P>0.05), but the renal cortex renin content [(8.72±1.98) ng/(mL·h) vs. (4.37±1.26) ng/(mL·h), P<0.05], AGT formation [(4.02±0.60) ng/mg vs. (2.59±0.42) ng/mg, P<0.01], ANGⅡ level [(313.8±48.76) pmol/L vs. (188.9±46.95) pmol/L, P<0.05] were increased significantly in HS, and the urinary AGT and ANGⅡ excretion rates increased significantly (P<0.05). Compared with HS, the plasma renin activity, angiotensinogen and ANGⅡ level were significantly increased (P<0.05), but the renal cortex renin content, AGT formation, ANGⅡ level significantly decreased (P<0.05), and the urinary AGT and ANGⅡ excretion rates decreased significantly in HS+L (P<0.05). The urinary AGT excretion rates were positively correlated with the AGT level in the renal cortex (P<0.05). Conclusion: Up-regulation of intarenal RAS may contribute to renal damage in high-salt induced hypertension rats. Urinary AGT may reflect the status of intrarenal RAS.

Key words: Sodium chloride, dietary, Renin-agiotensin system, Hypertension, Proteinuria, Angiotensinogen

[1] 陈楚云,孙蓬飞,赵静,贾佳,范芳芳,王春燕,李建平,姜一梦,霍勇,张岩. 北京社区人群促红细胞生成素相关因素及其与10年心血管疾病风险的关系[J]. 北京大学学报(医学版), 2023, 55(6): 1068-1073.
[2] 梁喆,范芳芳,张岩,秦献辉,李建平,霍勇. 中国高血压人群中H型高血压的比率和特征及与美国人群的比较[J]. 北京大学学报(医学版), 2022, 54(5): 1028-1037.
[3] 马麟,吴静依,李双成,李鹏飞,张路霞. 抗高血压药物对二氧化氮长期暴露与慢性肾脏病关联的修饰效应[J]. 北京大学学报(医学版), 2022, 54(5): 1047-1055.
[4] 皇甫宇超,杜依青,于路平,徐涛. 原发性醛固酮增多症术后高血压未治愈的危险因素[J]. 北京大学学报(医学版), 2022, 54(4): 686-691.
[5] 李志胜,钱浩楠,范田园. 熔融沉积成型3D打印卡托普利与氢氯噻嗪复方片剂的制备与体外评价[J]. 北京大学学报(医学版), 2022, 54(3): 572-577.
[6] 尹雪倩, 张晓玄, 文婧, 刘思奇, 刘欣然, 周若宇, 王军波. 荞麦、燕麦、豌豆复配对糖尿病大鼠血糖的影响[J]. 北京大学学报(医学版), 2021, 53(3): 447-452.
[7] 王双佳,王婷婷,王军波. 北京某高校医学院师生营养知信行水平及其影响因素[J]. 北京大学学报(医学版), 2020, 52(5): 881-885.
[8] 杨航,杨林承,张瑞涛,凌云鹏,葛庆岗. 合并高血压、冠心病、糖尿病的新型冠状病毒肺炎患者发生病死的危险因素分析[J]. 北京大学学报(医学版), 2020, 52(3): 420-424.
[9] 郑鸿尘,薛恩慈,王雪珩,陈曦,王斯悦,黄辉,江锦,叶莺,黄春兰,周筠,高文静,余灿清,吕筠,吴小玲,黄小明,曹卫华,严延生,吴涛,李立明. 基于大家系设计的静息心率与常见慢性病双表型遗传度估计[J]. 北京大学学报(医学版), 2020, 52(3): 432-437.
[10] 孟文颖,黄琬桐,张杰,焦明远,金蕾,靳蕾. 孕早期血清维生素E水平与妊娠期高血压疾病发病风险的关系[J]. 北京大学学报(医学版), 2020, 52(3): 470-478.
[11] 张晓圆,郭成成,玉应香,谢岚,常翠青. 高脂饲料诱导肥胖胰岛素抵抗大鼠模型的建立[J]. 北京大学学报(医学版), 2020, 52(3): 557-563.
[12] 刘颖,曾祥柱,王筝,张函,王希林,袁慧书. 三维动脉自旋标记技术评价抑郁合并高血压患者脑血流灌注[J]. 北京大学学报(医学版), 2019, 51(2): 260-264.
[13] 孙颖,靳蕾. 中国北方3县妊娠妇女血液锰浓度及其影响因素[J]. 北京大学学报(医学版), 2018, 50(3): 463-468.
[14] 刘雪芹, 闫辉, 邱建星, 张春雨, 齐建光, 张欣, 肖慧捷, 杨艳玲, 陈永红, 杜军保. 甲基丙二酸尿症相关肺高血压临床特点与基因突变[J]. 北京大学学报(医学版), 2017, 49(5): 768-777.
[15] 单娇,李宏宇,刘国峰,杨玄,董伟,简伟研,邓芙蓉,郭新彪. 大气污染对中老年高血压和心脑血管疾病患者卫生服务需求的影响:基于 CHARLS数据的分析[J]. 北京大学学报(医学版), 2016, 48(3): 460-464.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!