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首页> 外文期刊>Pediatric critical care medicine: a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies >Reversal of acute tacrolimus-induced renal vasoconstriction by theophylline in rats.
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Reversal of acute tacrolimus-induced renal vasoconstriction by theophylline in rats.

机译：茶碱可逆转他克莫司引起的急性他克莫司引起的肾血管收缩。

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OBJECTIVE: To determine whether theophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, reverses the acute declines in renal blood flow and glomerular filtration rate induced by high-dose tacrolimus in rats. DESIGN: Prospective, randomized, placebo-controlled experimental study. SETTING: University-based basic science research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: After mechanical ventilation and instrumentation under isoflurane and nitrous oxide anesthesia, animals received either tacrolimus 0.5 mg/kg intravenously or vehicle and 1 hr later either theophylline 4 mg/kg intravenously or vehicle. MEASUREMENTS AND MAIN RESULTS: By using radiolabeled microspheres, renal blood flow was measured in three groups: control (n = 5), tacrolimus plus vehicle (n = 6), and tacrolimus plus theophylline (n = 6) at four time points-baseline and 60, 75, and 90 mins after tacrolimus or vehicle (the latter two time points being 15 and 30 mins after theophylline or vehicle, respectively). Whole blood tacrolimus and serum theophylline concentrations were measured. In a separate group of animals, by using (51)Cr-EDTA, glomerular filtration rate was measured in two groups: tacrolimus plus vehicle (n = 5) and tacrolimus plus theophylline (n = 5) at baseline and over two consecutive 20-min time periods beginning 61 mins posttacrolimus. Urine flow rate also was measured. Following tacrolimus, both renal blood flow and glomerular filtration rate declined in parallel by approximately 33% and 50% from baseline after 75 and 90 mins, respectively (p <.05 by two-way repeated-measures analysis of variance). Theophylline completely reversed these tacrolimus-induced decreases in renal blood flow and glomerular filtration rate. Urine flow rate also increased in response to theophylline. CONCLUSIONS: Low-dose theophylline reverses tacrolimus-induced declines in renal blood flow and glomerular filtration rate observed in an acute model of tacrolimus toxicity. Theophylline's effect in chronic toxicity remains to be determined.
机译：目的：确定茶碱（一种非选择性腺苷受体拮抗剂和磷酸二酯酶抑制剂）是否可以逆转大剂量他克莫司引起的肾血流量和肾小球滤过率的急剧下降。设计：前瞻性，随机，安慰剂对照实验研究。地点：基于大学的基础科学研究实验室。受试者：成年雄性Sprague-Dawley大鼠。干预措施：在异氟烷和一氧化二氮麻醉下进行机械通气和器械干预后，动物接受他克莫司0.5 mg / kg静脉滴注或赋形剂给药，1小时后接受茶碱4 mg / kg静脉滴注或赋形剂给药。测量和主要结果：通过使用放射性标记的微球，在三个时间点基线测量了三组的肾血流量：对照组（n = 5），他克莫司加赋形剂（n = 6）和他克莫司加茶碱（n = 6）。他克莫司或媒介物后60、75和90分钟（后两个时间点分别是茶碱或媒介物后15和30分钟）。测量全血他克莫司和血清茶碱浓度。在另一组动物中，通过使用（51）Cr-EDTA，测量了两组的肾小球滤过率：他克莫司加赋形剂（n = 5）和他克莫司加茶碱（n = 5）在基线和连续两个20-距他克莫司61分钟的最短时间段。还测量了尿流速。他克莫司治疗后，肾血流量和肾小球滤过率在75分钟和90分钟后分别平行于基线分别下降了约33％和50％（通过双向重复测量方差分析，p <.05）。茶碱完全逆转了这些他克莫司引起的肾血流量和肾小球滤过率下降。尿流率也响应茶碱而增加。结论：在他克莫司毒性急性模型中观察到，低剂量茶碱可逆转他克莫司引起的肾血流量和肾小球滤过率下降。茶碱对慢性毒性的作用尚待确定。

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