小剂量纳洛酮对大鼠吗啡耐受的影响  

Effect of Low-dose Naloxone on Morphine Tolerance in Rats

作　　者：郭瑶[1] 孟凌新[1] 

机构地区：[1]中国医科大学附属盛京医院麻醉科,沈阳110004

出　　处：《中国医科大学学报》2009年第6期443-445,共3页Journal of China Medical University

摘　　要：目的观察小剂量纳洛酮对大鼠吗啡耐受的影响,并探讨其可能的机制。方法选择健康雄性Wistar大鼠20只,随机分为吗啡组(M组)和纳洛酮组(MN组),每组各10只。M组和MN组每12 h分别皮下注射吗啡10 mg/kg和吗啡10 mg/kg+纳洛酮10 ng/kg,连续7 d,制作大鼠吗啡耐受模型。第1次给药前测定甩尾潜伏期(TFL)作为基础值,以后第1,3,6,9,12,15次给药后30 min测定甩尾潜伏期。以甩尾潜伏期及最大镇痛效率(MPE)为指标观察吗啡耐受发生的情况。7 d后取大鼠导水管周围灰质(PAG)脑组织,采用免疫组化方法观察PAG脑组织蛋白激酶A(PKA)染色,比较两组染色情况。结果反复应用吗啡后,M组和MN组大鼠TFL值和MPE下降的速度不同。MN组与M组比较大鼠TFL值和MPE的下降速度缓慢(P<0.05)。PAG组织PKA免疫组化染色结果显示,M组与MN组相比PKA表达增加(P<0.05)。结论小剂量纳洛酮抑制大鼠吗啡耐受的形成。Objective To study the effect of low-dose naloxone on morphine tolerance in rats and explore the possible mechanism. Methods Twenty male Wistar rats were randomly divided into 2 groups （n =10 each group）：group M and group MN. The rats were subcutaneouly injected every 12 hours with 10 mg/kg of morphine in group M and 10 mg/kg of morphine and 10 ng/kg of naloxone in group MN for 7 days, respectively. The tail flick latency （TFL） before the injection of drugs was measured as the basal value, and 30 minutes after the first, third, sixth, ninth, twelfth, and fifteenth injection of drugs, the TFLs were measured respectively. TFL and the percentage of maximal possible effect （MPE） were used to evaluate morphine tolerance. The rats were killed after 7 days, and the brain tissue including periaqueductal gray （PAG） was sampled, Immunohistochemieal staining was performed to detect protein kinase A （PKA） in the brain tissue. Results TFL and MPE in groups M and MN significantly decreased after repeated injections of morphine, and they decreased more rapidly in group M than in group MN （P 〈 0.05 ）. The expression of PKA in group M was higher than that in group MN （P 〈 0.05 ）. Conclusion Low-dose naloxone could delay the development of morphine tolerance in rats.

关 键 词：吗啡 耐受 小剂量纳洛酮 蛋白激酶A 

分 类 号：R614[医药卫生—麻醉学]