摘要
目的探讨Ras相关的C3肉毒菌毒素底物1(Rac1)在孕期脂多糖暴露诱导子代大鼠血压升高中的作用及机制。方法 12只SD孕鼠随机均分为2组,于孕第8天、第10天、第12天接受等体积生理盐水或脂多糖(0.79mg/kg)腹腔注射,对应子代雄鼠编为对照组(n=18)和脂多糖组(n=18)。4周龄时断奶,5周龄起以袖尾法连续监测血压。16周龄每组随机选取6只进行Rac1特异性抑制剂NSC23766[4mg/(kg·d)]连续皮下注射,每周记录血压、尿钠代谢变化。20周龄时,2组各随机选取6只未接受抑制剂注射的大鼠用于连续监测血压至48周,其余处死、取材,并测定随机血糖、肌酐、尿素氮;HE及Masson染色观察肾脏病理改变;Western blot检测肾脏Rac1表达、胞浆盐皮质激素受体(c-MR)含量和核转位盐皮质激素受体(n-MR)等。结果与对照组比较,脂多糖组出生体质量较低,而20周龄体质量较高(均P<0.01)。20周龄时,与对照组比较,脂多糖组收缩压水平、肾脏Rac1表达和n-MR含量较高;而24h尿量、24h尿钠排泄量和c-MR含量较低(均P<0.01)。20周龄时,与脂多糖组比较,脂多糖+NSC23766组收缩压[(116.6±2.2)比(133.6±3.2)mm Hg]和n-MR含量(1.11±0.10比1.93±0.21)明显下降(均P<0.01);而24h尿量[(32.21±3.65)比(14.12±3.23)mL/(kg·d)]、24h尿钠排泄量[(1.44±0.22)比(0.50±0.18)mmol/(kg·d)]和c-MR含量(0.96±0.05比0.52±0.05)明显升高(均P<0.01)。结论孕期脂多糖暴露可致子代大鼠血压增高,尿钠排泄障碍,Rac1表达增高,Rac1-MR信号过度活化参与孕期脂多糖刺激诱导子代血压增高的过程。
Objective To explore the role of Ras related C3 botulinum toxin substrate 1 ）Racl） in prenatal lipopo- lysaccharides （LPS） exposure induced elevated blood pressure in rat offspring and the implied mechanisms. Methods Twelve pregnant Spregue-Dawley （SD） rats were randomly divided into two groups with intraperitoneal injections of equal volume of saline or LPS （0.79 mg/kg） at pregnant 8, 10 and 12 d. The corresponding male off- spring from each group served as control group （n=18} or LPS group （n=181. The offspring were weaned at 4- week-old and the blood pressures were detected continuously starting from 5-week old via tail-cuff method. At 16 weeks, 6 offspring rats were randomly selected from control and LPS groups and given subcutaneous injection of the specific inhibitor of Racl, NSC23766 4 [mg/（kg - d）] and the blood pressure and natriuresis were monitored week- ly. At 20 weeks, 6 offspring rats from each group that had not been given inhibitor were randomly selected for con tinuously monitoring blood pressure until 48-week-old; the rest offspring rats were euthanized, and the levels of ran- dom plasma glucose, creatinine and urea nitrogen were measured. Pathological changes of kidney were observed by HE and Masson staining. Western blot was used to detect expression of Rael, contents of cytoplasmic mineralo- corticoid receptor （e-MR） and mineralocorticoid receptor nuclear translocation （n-MR）. Results Compared with control group, LPS group showed lower birth weight but higher adult-weight at 20-week-old. At 20 weeks, com- pared with control group, LPS group showed significantly higher systolic blood pressure, Racl expression and n-MR content, and lower 24 h urine volume, 24 h urinary sodium and c-MR content （P〈0.01）. At 20 weeks, compared with LPS group, LPS＋ NSC23766 group showed significantly lower blood pressure [（116.6 ± 2.2） vs ）133.6 ± 3.2 ） mm Hg], n-MR content （ 1.11± 0.10 vs 1.93 ± 0.21 ）, and significantly higher 24 h urine volume [（32. 21± 3. 65） vs （14. 12±3. 23） mL/（kg · d）-1, urinary sodium [（1.44±0. 22） vs （0. 50±0. 18） mmol/（kg· d）] and c-MR content （0.96± 0.05 vs 0.52±0.05） {all P〈0.01 ）. Conclusion LPS exposure during pregnancy resulted in elevated blood pressure and natriuresis impairment in offspring rats. Increased expression of Racl and aberrant activation of Racl-MR signaling may be the implied mechanisms in prenatal LPS exposure induced elevated blood pressure in offspring.
作者
曹念
胡翠美
邓燚
郑硕
傅春江
曾春雨
CAO Nian, HU Cui-mei, DENG Yi, ZHENG Shuo, FU Chun-jiang, ZENG Chun-yu(Department of Cardiology, Chongqing Institute of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, Chin)
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2018年第2期132-137,共6页
Chinese Journal of Hypertension
基金
国家自然科学基金面上项目(81570380)
国家自然科学基金青年科学基金项目(81700375)资助
