β-血小板衍生生长因子信号通路在吗啡耐受机制中的作用

发布时间：2018-09-18 19:39

【摘要】：目的评价细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)和CAMP反应元件结合蛋白(cyclic AMP response element binding protein,CREB)信号通路在β-血小板衍生生长因子(beta platelet-derived growth factor,PDGF)受体介导的大鼠吗啡耐受中的作用。方法 36只健康雄性SD大鼠按随机数字表法分为6组(n=6):对照组(等渗盐水20μL)、吗啡组(吗啡15μg)、吗啡+伊马替尼组(吗啡15μg+伊马替尼10μg)、吗啡+PDGF-BB组(吗啡15μg+PDGF-BB 10ng)、伊马替尼组(伊马替尼10μg)、PDGF-BB组(PDGF-BB 10 ng)。各组分别鞘内注射药物20μL,1次/d,连续7 d。于给药前1d测定热缩足潜伏期(paw withdrawal latency,PWL)基础值,给药后1、3、5、7 d鞘内注射30 min后测定PWL,计算最大镇痛效应百分比(maximal possible effect,MPE)。第8天,各组大鼠鞘内单独注射吗啡15μg 30 min后测定PWL,计算MPE,测定PWL后取L4-5脊髓,Western blot法测定ERK、p-ERK、CREB和p-CREB的表达水平。结果吗啡组给药后第5、7天MPE值分别为(52.90±8.20)%和(15.1±3.80)%,较第1天[(100.00±0.00)%]明显降低(P0.05);吗啡+PDGF-BB组给药后第5、7天MPE值分别为(43.51±5.42)%和(14.81±3.60)%,较第1天[(100.00±0.00)%]明显降低(P0.05);而吗啡+伊马替尼组给药后第1、3、5、7天MPE值无明显变化;第8天单独鞘内注射15μg吗啡后,吗啡组、吗啡+PDGF-BB组和PDGFBB组MPE值分别为(16.22±2.51)%、(15.22±3.50)%(35.21±4.51)%,较对照组[(100.00±0.00)%]均明显降低(P0.05);6组大鼠脊髓ERK和CREB表达水平差异无统计学意义;吗啡组、吗啡+PDGF-BB组和PDGF-BB组大鼠脊髓磷酸化ERK和磷酸化CREB表达较对照组均上调(P0.05);吗啡+伊马替尼组大鼠脊髓磷酸化ERK和磷酸化CREB表达较吗啡组均下调(P0.05)。结论 PDGFR-β信号通路在吗啡耐受过程中具有重要作用,具体机制与激活下游ERK和CREB通路有关。
[Abstract]:Objective to evaluate the role of extracellular signal-regulated kinase (extracellular signal-regulated kinase,ERK) and CAMP response element binding protein (cyclic AMP response element binding protein,CREB) signaling pathway in 尾 -platelet-derived growth factor (beta platelet-derived growth factor,PDGF) receptor mediated morphine tolerance in rats. Methods 36 healthy male SD rats were randomly divided into 6 groups: control group (isotonic saline 20 渭 L), morphine group) (morphine 15 渭 g), morphine imatinib group (morphine 15 渭 g imatinib 10 渭 g), morphine PDGF-BB group), imatinib group (morphine 15 渭 g PDGF-BB 10ng) PDGF-BB group (10 渭 g imatinib) (PDGF-BB 10 ng).) Each group received intrathecal injection of 20 渭 L per day for 7 days. The basic values of (paw withdrawal latency,PWL were measured 1 day before administration and 30 min after intrathecal injection of PWL,. The maximum analgesic effect percentage (maximal possible effect,MPE) was calculated. On the 8th day, the levels of ERK,p-ERK,CREB and p-CREB were measured by PWL, and PWL after intrathecal injection of morphine (15 渭 g) for 30 min. The expression of ERK,p-ERK,CREB and p-CREB were determined by L4-5 spinal cord blot method. Results the MPE values in morphine group were (52.90 卤8.20)% and (15.1 卤3.80)%, respectively, which were significantly lower than those on day 1 [(100.00 卤0.00)%] (P0.05), and the MPE values in morphine PDGF-BB group were (43.51 卤5.42)% and (14.81 卤3.60) on the 7th day after administration, which were significantly lower than those on day 1 [(100.00 卤0.00)%] (P0.05). There was no significant change in the MPE value on the 7th day of the 3rd day of the first trimester. On the 8th day after intrathecal injection of 15 渭 g morphine alone, the MPE values of morphine group, morphine PDGF-BB group and PDGFBB group were (16.22 卤2.51), (15.22 卤3.50)% (35.21 卤4.51), respectively, which were significantly lower than those of control group [(100.00 卤0.00)%]. The expression of phosphorylated ERK and phosphorylated CREB in spinal cord of morphine PDGF-BB group and PDGF-BB group were all up-regulated than that of control group (P0.05), and the expression of phosphorylated ERK and phosphorylated CREB in morphine imatinib group was lower than that in morphine group (P0.05). Conclusion PDGFR- 尾 signaling pathway plays an important role in morphine tolerance, and the specific mechanism is related to activation of downstream ERK and CREB pathways.
【作者单位】：南京军区南京总医院麻醉科;
【基金】：南京军区南京总医院科研基金(2013029)
【分类号】：R965

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