姜黄素对大鼠脊髓Toll样受体4活化及吗啡镇痛耐受的影响  

Curcumin attenuates morphine antinociceptive tolerance through suppressing up-regulation of spinal Toll-like receptor 4 in rats

作　　者：高菲 郑少东 李轶聪 赵昱 

机构地区：[1]哈尔滨医科大学附属第二医院检验科,哈尔滨150086 [2]解放军211医院麻醉科,哈尔滨150080 [3]黑龙江省医院麻醉科,哈尔滨150036

出　　处：《解放军医学杂志》2017年第12期1056-1060,共5页Medical Journal of Chinese People's Liberation Army

基　　金：全军医学科技"十二五"科研课题(CWS11J006)~~

摘　　要：目的观察姜黄素对大鼠脊髓Toll样受体4(TLR4)活化及吗啡镇痛慢性耐受的影响并探讨其作用机制。方法健康清洁级SD大鼠60只,成功鞘内置管后随机分为生理盐水(NS)组、吗啡(MOR)组、姜黄素(Cur)组和吗啡+姜黄素(MOR+Cur)组,每组15只。MOR组和MOR+Cur组连续7d鞘内注射15μg吗啡建立吗啡慢性耐受动物模型,Cur组及MOR+Cur组连续7d鞘内注射100μg姜黄素,NS组连续7d鞘内注射10μl生理盐水。应用甩尾潜伏期法(TFL)及机械反射阈值法(MWT)观察鞘内注射姜黄素对吗啡镇痛耐受的影响并计算最大镇痛效应(MPE);应用免疫组织荧光染色法检测姜黄素对腰段脊髓小胶质细胞活化的影响;应用Real-time PCR及Western blotting检测姜黄素对腰段脊髓TLR4 mRNA和蛋白表达的影响。结果连续7d鞘内注射吗啡后,MOR+Cur组大鼠MPE明显高于MOR组(P<0.05);鞘内注射姜黄素和生理盐水均未产生明显镇痛作用,Cur组MPE与NS组比较差异无统计学意义(P>0.05)。与NS组比较,MOR组大鼠腰段脊髓背角小胶质细胞明显增多,TLR4 mRNA和蛋白表达明显增加(P<0.05),而Cur组腰脊髓背角小胶质细胞数量及TLR4 mRNA和蛋白表达差异无统计学意义(P>0.05)。与MOR组比较,MOR+Cur组大鼠腰段脊髓背角小胶质细胞明显减少,TLR4 mRNA和蛋白表达明显减少(P<0.05)。结论姜黄素可能通过抑制脊髓内TLR4的表达而拮抗大鼠对吗啡镇痛的慢性耐受。Objective To investigate the effects of curcumin （Cur） on activation of spinal Toll-like receptor 4 （TLR4） and on the chronic antinociceptive tolerance of morphine. Methods Sixty male Sprague-Dawley rats with successful intrathecal catheterization were randomly divided into four groups （n=15）： saline （NS） group; morphine （MOR） group; curcumin （Cur） group and morphine plus curcumin （MOR＋Cur） group. A morphine tolerance model of rats was induced by intrathecal injection of morphine 15t^g~ once a day for 7 consecutive days in MOR and MOR＋Cur group; 1001~g curcumin was administered intrathecally once a day for 7 consecutive days in Cur and MOR＋Cur group, 101~1 saline was administered intrathecally once a day for 7 consecutive days in NS group. The effect of curcumin intrathecal catheterization on morphine antinociceptive tolerance was explored by the tail flick latency （TFL） method and mechanical withdrawal threshold （MWT）, and then the maximum possible potential effect （MPE） was calculated. The immunofluorescence staining method was applied to detect the effect of curcumin on the activation of lumbar spinal microglia. Real-time PCR and Western blotting were used to evaluate the effect of curcumin on the expression ofmRNA and protein of spinal TLR4. Results The %MPE TFL and %MPE MWT increased significantly in MOR＋Cur group than in MOR group （P〈0.05） after 7 days of intrathecal injection of morphine, intrathecal injection of curcumin and saline failed to induce analgesic effect. There was no significant difference in MPE between Cur group and NS group （P〉0.05）. The lumbar spinal microglia increased markedly and the expressions of polyclonal antibody IBA-1 and TLR4 were significantly up-regulated in MOR group than in NS group （P〈0.05）. The lumbar spinal microglia decreased obviously and the expressions of IBA-1 and TLR4 were significantly down-regulated in MOR＋Cur group as compared with that in MOR group （P〈0.05）, but there was no significant d

关 键 词：吗啡 镇痛耐受 姜黄素 TOLL样受体4 脊髓 

分 类 号：R614[医药卫生—麻醉学]