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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 investigate the effect of pregnancy-induced inflammatory stimuli on the expression and function of renal angiotensin Ⅱ type 1 receptor (AT1R) in offspring rats, and to provide a new basis for the prevention and treatment of hypertension. Methods Twenty female SD rats weighing 250-280 g (body weight 250-280 g) and 8 males (250-280 g) weighing 20-2 weeks were mated 2: 1 and 12 pregnant rats were randomly divided into LPS group and control group Group (6 each). LPS group were injected intraperitoneally with lipopolysaccharide 0.79 mg / kg on the 8th, 10th and 12th day of pregnancy respectively, and the control group was injected intraperitoneally with the same volume of normal saline. Non-invasive rat tail manometry was used to monitor offspring blood pressure. Six male rats (20 weeks old, 250-280 g) were randomly selected from offspring of LPS group and control group for experiment. Metabolic cage collected 24 h urine , AT1R function was detected by perfusing the adrenal artery with angiotensin II type 1 receptor antagonist (candesartan), AT1R mRNA expression in offspring rat kidney was detected by qRT-PCR, Of AT_1R protein expression. Results With the change of age, the blood pressure of offspring rats in LPS group was significantly higher than that in the control group. 24 h urine test results showed that the urine volume and urinary sodium excretion rate in the offspring rats in LPS group were significantly lower than those in control group (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). Adrenal artery perfusion of candesartan, LPS offspring of rats in the role of natriuresis urinary output, urinary sodium excretion were significantly higher than the control group [(6.5 ± 0.6) μL / min vs (11.7 ± 1.3) μL /min, (856.8 ± 61.6) μmol / min vs (1282.4 ± 89.9) μmol / min, P <0.05]. The expression of AT1R mRNA and protein in the kidney of LPS group was significantly higher than that of control group [(1.31 ± 0.07) vs (0.56 ± 0.06) vs (1.41 ± 0.03) vs (0.58 ± 0.12), P <0.05. Conclusion LPS exposure during pregnancy leads to elevated blood pressure in offspring. The mechanism may be related to the increased expression of AT_1R and its function in offspring rats, which may lead to the water and sodium retention in the body.