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鞘内注射腺苷A_1受体激动剂对吗啡和可乐定镇痛作用的影响 被引量:3

Analgesic effect of adenosine A_1 receptor agonist injected into the brainstem medial pontine reticular formation in rats
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摘要 目的观察鞘内注射腺苷A_1受体激动刺笨基异丙基腺苷(R-P1A)对吗啡和可乐定镇痛作用的影响。方法健康雄性SD大鼠,鼠龄8~10周,体重250~300 g.鞘内置管成功的85只大鼠随机分为17组,每组5只,对照组、R-PIA0.4组、R-PIA0.8组、R-PIA1.0组、茶碱组、吗啡2.0组、吗啡5.0组、可乐定2.0组、可乐定15.0组、R-PIA+吗啡2.0组、R-PIA+吗啡5.0组、R-PIA+可乐定2.0组、R- PIA+可乐定15.0组、可乐定+吗啡组均鞘内注射生理盐水,15min后分别注射生理盐水、R-PIA 0.4μg、R-PIA 0.8μg、R·PIA 1.0μg、茶碱50μg、吗啡2.0μg、吗啡5.0μg、可乐定2.0μg、可乐定15.0μg、R- P1A 0.4μg+吗啡2.0μg、R-PIA 0.4μg+吗啡5.0μg、R-PIA 0.4μg+可乐定2.0μg、R-PIA 0.4μg+可乐定15.0μg、可乐定2.0μg+吗啡2.0μg;R-PIA+吗啡+茶碱组、R-PIA+可乐定+茶碱组、可乐定+吗啡+茶碱组鞘内注射茶碱50μg,15 min后分别注射R-PIA 0.4μg+吗啡5.0μg、R-PIA 0.4μg+可乐定15.0μg、可乐定2.0μg+吗啡2.0μg,每次给药容积均为10μl、注药后5、10、20、30、40、60 min时测定大鼠热辐射甩尾反应潜伏期(TFL),用最大效应百分比(MPE)[(注药后TFL-TFL的基础值)/(10.0- TFL的基础值)×100%]评价镇痛效果。结果高剂量R-PIA、吗啡、可乐定可升高MPE,R-PIA可增强吗啡、可乐定的镇痛作用,可被茶碱完全阻断,吗啡可增强可乐定的镇痛作用,可被茶碱部分阻断;可乐定可增强吗啡的镇痛作用。结论大鼠鞘内注射R-PIA可增强吗啡和可乐定的镇痛作用,其机制可能与活化脊髓内腺苷受体有关。 Objective To investigate the analgesic effect of adenosine A1 receptor agonist R( - )-N6-(2- phenyl-isopropyl)-adenosine (R-HA) injected into the brainstem medial pontine reticular formation (mPRF) and the underlying mechanism. Methods Sixty male SD rats aged 8-10 weeks weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal 10% chloral hydrate 300 mg. kg^-1. A 24-gauge stainless steel cannula was inserted into mPRF on one side using a stereotaxic apparatus. One week after cannulation the animals were randomly divided into 12 groups ( n = 5 each) : group Ⅰ control received normal saline (NS) 0.3 μl; group Ⅱ ,Ⅲ, Ⅳ received R-HA 0.5, 1.0 and 2.0 μg in NS 0.3 μl respectively; group Ⅴ theophylline (an adenosine receptor antagonist) 5.0 μg ; group Ⅵ 8-cyclopentyl- 1,3-dipropylxanthine ( DPCPX, an adenosine A l receptor antagonist) 1.0 μg; group Ⅶ gliben-clamide (an ATP-sensitive k+ channel blocker) 5.0μg; group Ⅷ 4-aminopyridine (4-AP, a voltage dependent K^+ -channel blocker) 5.0 μg; group Ⅸ theophylline 5.0 μg + R-PIA 2.0 μg; group Ⅹ DPCPX 1.0 μg + R-HA 2.0 μg; group Ⅺ glibenclamide 5.0 μg + R-HA 2.0 μg and group Ⅻ 4- AP 5.0 μg + R- PIA 2.0 μg. All the drugs injected into mPRF were in 0.3 μl of NS. In group Ⅸ -Ⅻ R- HA 2.0 μg was administered 15 min after pretreatment with theophylline, DPCPX, glibenclamide or 4-AP. Analgesia was determined using the tail-flick latency (TFL) (the time between the onset of the radiant heat stimulus and voluntary tail withdrawal) at 5, 15, 30, 45, 60 and 90 min after R-HA injection into mPRF. Maximal possible effect (MPE) was calculated. MPE (TFL after drug - baseline TFL) / ( 10.0 - baseline TFL) ~ 100 %. Results R-PIA 0.5-2.0μg injected into mPRF produced significant analgesia in a dose-dependent manner. Pretreatment with theophylline or DPCPX completely reversed the analgesic effect of R-PIA while pretreatment with glibenclam
出处 《中华麻醉学杂志》 CAS CSCD 北大核心 2006年第8期688-691,共4页 Chinese Journal of Anesthesiology
关键词 腺苷 吗啡 可乐定 蛛网膜下腔 镇痛 Adenosine Morphine Clonidine Subarachnoid space Analgesia
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