孕期炎症刺激对子代大鼠肾脏血管紧张素Ⅱ1型受体表达及功能的影响  

Effect of LPS exposure during pregnancy on expression and function of renal angiotensin Ⅱ type 1 receptor in adult rat offsprings

作　　者：彭晓玉[1] 罗浩[1] 王新全[1] 傅春江[1] 曾春雨[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所心血管内科,重庆400042

出　　处：《第三军医大学学报》2016年第16期1815-1819,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81570380;81470936)~~

摘　　要：目的探讨孕期炎症刺激对子代大鼠肾脏血管紧张素Ⅱ1型受体（angiotensinⅡtype 1receptor,AT_1R）表达及功能的影响,为高血压的防治提供新的依据。方法 20周龄SD大鼠雌性（体质量250～280 g）16只、雄性（体质量250～280 g）8只2∶1交配,选择12只孕鼠随机分成脂多糖（LPS）组和对照组（各6只）。LPS组分别于孕8、10、12 d腹腔注射脂多糖0.79 mg/kg,对照组腹腔注射同等体积生理盐水。采用无创鼠尾测压仪监测子代血压,分别从LPS组和对照组子代中随机选取6只雄性大鼠（20周龄,250～280 g）用于实验,代谢笼收集24 h尿液,肾上腺动脉灌注血管紧张素Ⅱ1型受体拮抗剂（坎地沙坦）检测AT_1R功能,实时荧光定量（qRT-PCR）测定子代大鼠肾脏的AT_1R mRNA表达,免疫印迹检测子代大鼠肾脏的AT_1R蛋白表达。结果 LPS组子代大鼠随着周龄的变化,血压明显高于对照组子代大鼠。24 h尿液检测结果显示,LPS组子代大鼠的尿量及尿钠排泄率均低于对照组,分别为（24.6±1.8）m L vs（19.5±1.5）m L、（750.7±48.2）μmol/d vs（568.4±52.5）μmol/d（P〈0.05）。肾上腺动脉灌注坎地沙坦后,LPS组子代大鼠的排钠利尿作用即尿量、尿钠排泄率均明显高于对照组[（6.5±0.6）μL/min vs（11.7±1.3）μL/min,（856.8±61.6）μmol/min vs（1 282.4±89.9）μmol/min,P〈0.05]。LPS组子代大鼠肾脏AT_1R mRNA及蛋白的表达均显著高于对照组[（1.31±0.07）vs（0.56±0.06）,（1.41±0.03）vs（0.58±0.12）,P〈0.05]。结论孕期LPS暴露导致子代血压升高,其机制可能与子代大鼠肾脏AT_1R表达及功能增强,引起体内水钠潴留有关。Objective To explore the effect of lipopolysaccharide（ LPS） exposure during pregnancy on the expression and function of renal angiotensin Ⅱ type 1 receptor（ AT_1R） in the adult rat offsprings,and provide new evidence for prevention and treatment of hypertension. Methods SD female rats（ 20 weeks old）with body weight of 250 ～ 280 g were mated with SD male rats（ 20 weeks old） with body weight of 250 ～280 g,and the female rats with vaginal plug of white crystalline particles were identified as the pregnant rats.Twelve pregnant SD rats were randomly divided into LPS group（ n = 6） and control group（ n = 6）. On days8,10,and 12 after gestation,the LPS group was treated by intraperitoneal injection of 0. 79 mg / kg LPS,while the control group was injected with the equal volume of normal saline. Blood pressure of the offsprings was measured by noninvasive tail pressure instrument,and the urine of the offsprings was collected by metabolic cage. The renal AT_1 R function of the offsprings was determined by suprarenal artery administration of AT_1 R antagonist candesartan. The renal AT_1 R mRNA level was measured by qRT-PCR,while the protein expression was detected by Western blotting. Results With the increasing age,the blood pressure of the offsprings was significantly higher in the LPS group than in the control group. 24-h urine results showed that the urine volume and urinary sodium excretion rate of the offsprings from the LPS group were lower than those from the control group（ 24. 6 ± 1. 8 vs 19. 5 ± 1. 5 m L,750. 7 ± 48. 2 vs 568. 4 ± 52. 5 mol / d,P〈 0. 05）.The candesartan-induced natriuretic and diuretic effects in the offsprings from the LPS group were stronger than those in the offsprings from the control group（ 6. 5 ± 0. 6 vs 11. 7 ± 1. 3 m L,856. 8 ± 61. 6 vs 1 282. 4 ± 89. 9mol / min,P 〈0. 05）. The expression of AT_1 R at mRNA and protein levels in the offsprings from the LPS group were higher than those from the control group（ 1. 31 ± 0. 07 vs 0. 56 ± 0. 06,

关 键 词：孕期 脂多糖 子代 高血压 血管紧张素Ⅱ1型受体 

分 类 号：R341[医药卫生—基础医学] R364.5