鞘内注射重组大鼠白细胞介素18对大鼠吗啡耐受形成的影响  

Effect of intrathecal recombinant rat interleukin-18 On development of morphine tolerance in rats

作　　者：谢军明[1] 李永乐[1] 舒银银[1] 刘健[1] 嵇晴[1] 朱四海[1] 张利东[1] 李伟彦[1] 

机构地区：[1]南京大学医学院临床学院南京军区南京总医院麻醉科,210002

出　　处：《中华麻醉学杂志》2013年第2期152-155,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学青年基金（81102514）

摘　　要：目的评价鞘内注射重组大鼠白细胞介素18（rrIL-18）对大鼠吗啡耐受形成的影响。方法清洁级健康雄性sD大鼠，体重150-180g，鞘内置管成功后，采用随机数字表法，将其分为4组（n=12），Ⅰ组鞘内注射PBS溶液20μl，Ⅱ组、Ⅲ组和Ⅳ组分别鞘内注射20μl含rrIL-180．2、2．0、10．0μg的PBS溶液，1次／d，连续7d。分别在鞘内给药前1d和给药后第8、10、12天，尾静脉注射吗啡4mg／kg，吗啡注射前及注射后45min时测定辐射热缩爪潜伏期，计算吗啡的最大可能镇痛效应百分比，第12天行为学测试结束后处死动物，取脊髓腰膨大，采用免疫荧光染色法测定脊髓星形胶质细胞标志物胶质纤维酸性蛋白的表达，采用Westernblot法检测磷酸化细胞外信号调节激酶42／44（p-ERK42／44）的表达。结果与Ⅰ组比较，Ⅲ组和Ⅳ组第8、10、12天基础辐射热缩爪潜伏期缩短，最大可能镇痛效应百分比降低，第12天脊髓胶质纤维酸性蛋白和p-ERK42／44表达上调（P〈0．05）。结论大鼠鞘内连续注射7drrIL-182．0、10．0μg可促进吗啡耐受形成，可能与活化脊髓星形胶质细胞有关。Objective To evaluate the effect of intrathecal （IT） recombinant rat interleukin-18 （rrIL-18） on the development of morphine tolerance in rats. Methods Forty-eight male Sprague-Dawley rats in which IT catheters were successfully implanted without complications, weighing 150-180 g, were randomly divided into 4 groups （ n = 12 each）. The rats were anesthetized with intraperitoneal 2% pentobarbital 50 mg/kg. Group Ⅰ re- ceived IT phosphate buffer solution 20 μl once a day for 7 consecutive days. GroupsⅡ -Ⅳ received IT phosphate buffer solution 20 μl containing rrIL-18 0.2, 2.0 and 10.0 μg once a day for 7 consecutive days, respectively. Morphine 4 mg/kg was injected via the tail vein on 1 day before IT administration and 8, 10, 12 days after IT ad- ministration. Paw withdrawal latency to thermal stimuli （PWTL） was measured before morphine injection and 45 min after morphine injection. Maximum analgesic effect （MPE） was calculated. The animals were sacrificed at day 12 after behavioral measurement and the lumbar enlargement segments of the spinal cord were removed for determi- nation of the expression of glial fibrillary acidc protein （GFAP） （by immuno-fluorescence） and phosphorylated ex- tracellular signal-regulated kinase 42/44 （p-ERK42/44） （by Western blot）. Results Compared with group Ⅰ , PWTL and MPE were significantly decreased on 8, 10, 12 days after IT administration and the expression of GFAP and p-ERK42/44 was up-regulated on 12 days after IT administration in groups Ⅲ and Ⅳ （ P 〈 0.05）. Conclu- sion IT injection of rrIL-18 2.0 and 10.0 gg for 7 days can promote the development of morphine tolerance possi- bly through activating astrocytes in spinal cord.

关 键 词：白细胞介素18 注射 脊髓 吗啡 药物耐受性 

分 类 号：R614[医药卫生—麻醉学]