急性实验性诱导内毒素血症后一氧化氮途径的种属特异性调节
Species-specific modulation of the nitric oxide pathway after acute experimentally induced endotoxemia.
作者信息
Bachetti Tiziana, Pasini Evasio, Suzuki Hisanori, Ferrari Roberto
机构信息
Cardiovascular Pathophysiology Research Centre, Foundation Salvatore Maugeri, IRCCS, Gussago, Brescia, Italy.
出版信息
Crit Care Med. 2003 May;31(5):1509-14. doi: 10.1097/01.CCM.0000063269.35714.7E.
OBJECTIVE
The derangement of the nitric oxide pathway is an important contributing factor to the pathogenesis of septic shock. The aim of this study was to investigate potential differences in modulation of such a pathway in two experimental models of endotoxemia.
DESIGN
Prospective, randomized, placebo-controlled animal investigation.
SETTING
Cardiovascular research laboratory.
SUBJECTS
Male, anesthetized, and mechanically ventilated New-Zealand rabbits (n = 24) and Sprague-Dawley rats (n = 24).
INTERVENTIONS
After pretreatment with 1400W (1 mg kg(-1) subcutaneously), an inhibitor of inducible nitric oxide synthase, animals received an intravenous bolus of Escherichia Coli lipopolysaccharides (5 mg kg(-1)). After 4 hrs, lungs, myocardial left ventricles, and aortas were collected.
MEASUREMENTS AND MAIN RESULTS
Blood mean arterial pressure, pH, and nitrite/nitrate were monitored. Nitric oxide in the exhaled air was measured by chemiluminescence. Tissue activity of both constitutive nitric oxide synthase and inducible nitric oxide synthase was determined by measuring the conversion of [3H]L-arginine to [3H]L-citrulline. In lipopolysaccharide-treated animals, both mean arterial pressure (after 60 to 90 mins) and blood pH (after 4 hrs) decreased with respect to baseline values. 1400W prevented lipopolysaccharide-induced hypotension only in rats (p <.01). Exhaled nitric oxide decreased in lipopolysaccharide-treated rabbits by 120 mins (from 12.6 +/- 0.6 to 8.4 +/- 0.6 ppb, p <.01) and remained low until the end of the experiment (p <.01 vs. baseline). Conversely, exhaled nitric oxide increased in lipopolysaccharide-treated rats by 120 mins (from 0.4 +/- 0.1 to 5.3 +/- 1.7 ppb, p <.01) and reached a plateau by 210 mins (19.8 +/- 3.1 ppb, p <.01 vs. baseline). 1400W prevented the lipopolysaccharide-induced increase in exhaled nitric oxide and blood nitrite/nitrate in rats (p <.05). Inducible nitric oxide synthase activity increased in endotoxemic rabbit heart (0.19 +/- 0.05 vs. 0.07 +/- 0.02 pmol L-citrulline/min/mg protein in the control group, p <.05) and in all rat tissues, being more striking in the lungs (25.00 +/- 0.01 vs. 0.19 +/- 0.04 pmol L-citrulline/min/mg protein in the control group, p <.001).
CONCLUSIONS
The nitric oxide pathway is differently modulated between endotoxemic rabbits and rats.
目的
一氧化氮途径紊乱是脓毒性休克发病机制中的一个重要促成因素。本研究旨在探讨在内毒素血症的两种实验模型中该途径调节的潜在差异。
设计
前瞻性、随机、安慰剂对照动物研究。
地点
心血管研究实验室。
对象
雄性、麻醉且机械通气的新西兰兔（n = 24）和斯普拉格-道利大鼠（n = 24）。
干预措施
用诱导型一氧化氮合酶抑制剂1400W（1 mg·kg⁻¹皮下注射）进行预处理后，动物静脉推注大肠杆菌脂多糖（5 mg·kg⁻¹）。4小时后，收集肺、心肌左心室和主动脉。
测量指标及主要结果
监测平均动脉压、pH值和亚硝酸盐/硝酸盐水平。通过化学发光法测量呼出气体中的一氧化氮。通过测量[³H]L-精氨酸向[³H]L-瓜氨酸的转化来测定组成型一氧化氮合酶和诱导型一氧化氮合酶的组织活性。在脂多糖处理的动物中，平均动脉压（60至90分钟后）和血液pH值（4小时后）相对于基线值均降低。1400W仅在大鼠中预防了脂多糖诱导的低血压（p <.01）。脂多糖处理的兔子呼出的一氧化氮在120分钟时降低（从12.6±0.6降至8.4±0.6 ppb，p <.01），并在实验结束前一直保持较低水平（与基线相比p <.01）。相反，脂多糖处理的大鼠呼出的一氧化氮在120分钟时增加（从0.4±0.1升至5.3±1.7 ppb，p <.01），并在210分钟时达到平台期（19.8±3.1 ppb，与基线相比p <.01）。1400W预防了脂多糖诱导的大鼠呼出一氧化氮和血液中亚硝酸盐/硝酸盐的增加（p <.05）。内毒素血症兔心脏中诱导型一氧化氮合酶活性增加（0.19±0.05对对照组的0.07±0.02 pmol L-瓜氨酸/分钟/毫克蛋白，p <.05），并且在所有大鼠组织中均增加，在肺中更为显著（25.00±0.01对对照组的0.19±0.04 pmol L-瓜氨酸/分钟/毫克蛋白，p <.001）。
结论
内毒素血症的兔子和大鼠之间一氧化氮途径的调节存在差异。
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