摘要
目的观察慢性吗啡耐受大鼠脊髓背角神经元磷酸化突触素Ⅰ（p-Synapsin Ⅰ）表达的变化。方法雄性SD大鼠45只，体重150～180g，月龄1～2月，随机分为5组（n=9）：假手术组（S组）、生理盐水组（NS组）、吗啡组（M组）、氯胺酮组（K组）和吗啡＋氯胺酮组（M＋K组）。除S组外，所有大鼠均行鞘内置管，恢复3d后鞘内给药，NS组给予生理盐水40出，M组给予吗啡20μg，K组给予氯胺酮30μg，M＋K组分别给予吗啡20μg及氯胺酮30μg，2次／d，连续7d。于给药前（T0，基础状态）、给药后1、3、5、7d及停药后1d（T1-5）时测定机械缩爪阈值（PWT）与热缩爪潜伏期（PWL），最后一次测定痛阈后处死大鼠，取L3～6脊髓背角，测定p-SynapsinⅠ（Sei603）的表达。结果与基础值比较，M组T1,2时PwT升高，T4，5时PWT降低，T1～3时PWL延长，T5时PWL缩短，M＋K组T1～5时PWT升高，PWL延长（P〈0．05）。与S组和NS组比较，M组T1,2时PWT升高，T4,5时PWT降低，T1-3时PWL延长，T5时PWL缩短，M＋K组T1～5时PWT升高，PWL延长（P〈0．05），K组PWT和PWL差异无统计学意义（P〉0．05）。与M组比较，M＋K组T2-5时PWT升高，T3-5时PWL延长（P〈0．05）。与S组和NS组比较，M组和M＋K组p-Synapsin Ⅰ（Set603）表达上调（P〈0．05），K组p-Synapsin Ⅰ（Ser603）表达差异无统计学意义（P〉0．05）；与M组比较，M＋K组p-Synapsin Ⅰ（Set603）表达下调（P〈0．05）。结论脊髓背角神经元Synapsin Ⅰ的磷酸化参与了大鼠慢性吗啡耐受的形成，吗啡促进Synapsin Ⅰ磷酸化的部分机制与激活N-甲基-D-天冬氨酸受体有关。
Objective To investigate the change in the expression of phosphorylated synapsin Ⅰ in the spinal dorsal horn following chronic morphine tolerance in rats. Methods Forty-five 1-2 month old male SD rats weighing 150-180 g were randomly divided into 5 groups （ n = 9 each） ： group Ⅰ sham operation （group S） ; group Ⅱ normal saline （group NS） ; group Ⅲ morphine （group M） ; group Ⅳ Ketamine （group K） and group Ⅴ M ＋ K. An intrathecal （IT） catheter was placed in the subarachnoid space at L3.4 interspace in group Ⅱ- Ⅴ . Animals showing motor or sensory dysfunction after surgery were excluded. Three days after surgery NS 40 μl, morphine 20 μg, ketamine 30 μg and morphine 20 μg ＋ ketamine 30μg were injected IT twice a day for 7 consecutive days in group Ⅱ , Ⅲ , Ⅳ and Ⅴ respectively. 50% paw withdrawal threshold （PWT） to mechanical stimulus and paw withdrawal latency （PWL） to noxious thermal stimulus were measured before （T0 , baseline）, on the 1st, 3rd, 5th and 7th day of IT drug administration （ T1-4 ） and at 1 day after IT drug administration （ T5 ） . The animals were sacrificed after last pain threshold measurement. The lumbar segment （ L3-6 ） was removed for determination of the expression of phosphorylated synapsin Ⅰ protein. Results In group M, PWT to mechanical stimulus was increased at T1-2, returned to the baseline level at T3 and decreased at T4,5, and PWL to noxious thermal stimulus was prolonged at T1-3 , returned to the baseline level at T4 and shortened at T5 as compared to the baseline value at To indicating successful establishment of morphine tolerance. In group M ＋ K, PWT to mechanical stimulus was increased and PWL to noxious thermal stimulus was prolonged at T1-5 as compared to the baseline value, indicating inhibition of morphine tolerance by ketamine. The expression of phosphorylated synapsin （Ser 603 ） was significantly higher in group M and M ＋ K than in group S, and was significantly lower in group M ＋ K than in group M. Conclusion The phosphorylated synapsin Ⅰ in the spinal dorsal horn may be involved in the development of chronic morphine tolerance which is partly mediated by NMDA receptor.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2010年第2期155-158,共4页
Chinese Journal of Anesthesiology
