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目的 研究神经元型一氧化氮合酶(nNOS)抑制剂7-硝基吲唑(7-NI)对大鼠异氟醚MAC的影响。方法 30只雄性SD大鼠,随机分为6 组(每组5 只)。大鼠置于密闭麻醉系统中,按标准夹尾法测定异氟醚MAC。每只鼠测定基础MAC后,随机经腹腔注射3m l花生油,或20、60、80、120或250m g·kg- 1 7-NI(溶于3m l花生油),30 分钟后测定MAC值。选120m g·kg- 1 7-NI组大鼠再腹腔注射500m g·kg- 1L-精氨酸,15分钟后测定MAC值。结果 20~250m g·kg- 1 7-NI显著降低异氟醚MAC,分别较基础MAC下降(15.6±2.3)% 、(21.9±2.1)% 、(29.9±2.5)% 、(30.4±1.7)% 、(29.8±3.3)% ,当7-NI剂量超过80m g·kg- 1时出现封顶效应。500m g·kg- 1 L-精氨酸可完全逆转120m g·kg- 1 7-NI降低MAC效应。结论 抑制中枢nNOS活性,可增强异氟醚麻醉效能,提示中枢NO信息途径可能在全麻药作用分子机制中起作用。
Objective To investigate the effect of 7-nitroindazole (7-NI), a neuronal nitric oxide synthase (nNOS) inhibitor, on isoflurane MAC in rats. Methods Thirty male SD rats were randomly divided into 6 groups (5 in each group). Rats were placed in a closed anesthesia system, according to standard clamp tail method for the determination of isoflurane MAC. After each rat was assayed for basal MAC, MACs were randomly injected either 3 ml peanut oil or 20, 60, 80, 120 or 250 mg kg-1 7-NI (dissolved in 3 ml peanut oil) per ip. The rats in the 120 m g · kg-1 7-NI group were injected intraperitoneally with 500 mg · kg -1 L-arginine, and MAC values were measured after 15 minutes. Results The MAC of isoflurane decreased significantly from 20 to 250 m g · kg-1 7-NI (15.6 ± 2.3%, 21.9 ± 2.1%, 29.9 ± 2.5%, (30.4 ± 1.7)% and (29.8 ± 3.3)%, respectively. The capping effect occurred when the dose of 7-NI exceeded 80 m g · kg-1. 500m g · kg -1 L-arginine can completely reverse 120m g · kg-1 7-NI reduce MAC effect. Conclusion Inhibition of central nNOS activity enhances the anesthetic efficacy of isoflurane, suggesting that the central NO signaling pathway may play a role in the molecular mechanism of general anesthetic action.