孕期脂多糖刺激诱导子代大鼠高血压的机制研究

摘要

Objective To explore the mechanism of hypertension caused by maternal exposure to lipopolysaccharide in adult offspring rats. Methods Nulliparous,pregnant,time-matched SD rats were randomly divided into two groups(n = 3):control group and LPS group. On the pregnant day 8,10 and 12,rats in control group and LPS group were administered intraperitoneally with saline 0.5 mL or LPS 0. 79 mg/kg, respectively. Thesystolic blood pressure was measured in offspring once three weeks from 7 weeks of age to 25 weeks of age. The plasma renin activity and angiotensin Ⅱ concentration were measured in adult offspring rats at 7,16 and 25 weeks of age,intrarenal renin was assessed by real-time PCR, AT1-R protein expression was assessed by Western blot and angiotensin Ⅱ-positive cells were determined with immunohistochemical staining. Results The blood pressure in offspring of LPS-treated rats increased constantly and reached hypertensive level at 24 weeks of age. The intrarenal renin mRNA expression and the number of angiotensin Ⅱ-positive cells increased at 7,16 and 25 weeks of age,while the AT1-R protein expression decreased. The plasma renin activity and angiotensin Ⅱ were unchanged. Conclusion Maternal expos s ure to lipopolysaccharide activates intrarenal renin-angiotensin system in adult offspring rats.%目的 探讨孕期脂多糖刺激诱导子代大鼠(简称子鼠)高血压的机制研究.方法 将SD孕鼠6只随机分为两组.对照组 3只:腹腔注射无菌生理盐水 0.5 mL;脂多糖组 3只:腹腔注射脂多糖,剂量为0.79 mg/kg.分别在孕期第8、10、12天08∶00～09∶00 进行腹腔注射.子鼠出生后,观察7～25周龄子鼠血压的变化和肾组织肾素mRNA表达、血管紧张素Ⅱ1型受体(AT1-R)的蛋白表达以及肾组织血管紧张素Ⅱ(AngⅡ)阳性细胞表达.结果 与对照组相比,脂多糖组子鼠血压逐渐升高,至24周龄时达到高血压水平.血浆肾素活性和AngⅡ浓度无变化.7、16、25周龄子鼠肾内肾素mRNA表达和AngⅡ阳性细胞数与对照组相比明显增高,并与血压呈正相关;AT1-R的蛋白表达与对照组相比降低,与肾素mRNA表达呈负相关.结论 孕期暴露于脂多糖引起子代成年大鼠肾组织肾素-血管紧张素系统活性增高,这可能是血压升高的一个机制.