脊髓P2X 4受体在大鼠慢性吗啡耐受形成中的作用  

Role of Spinal P2x4 Receptor In Process of Chronic Morphine Tolerance in Rats

作　　者：董良[1] 曾金[1] 曹健斌[2] 陈丽红[1] 黄一丹[1] 韦晓林 

机构地区：[1]广西壮族自治区柳州市人民医院麻醉科,广西柳州545006 [2]广西壮族自治区柳州市人民医院胸外科,广西柳州545006

出　　处：《医学临床研究》2015年第6期1056-1059,共4页Journal of Clinical Research

基　　金：广西卫生厅自筹课题（Z2014411）

摘　　要：【目的】观察慢性吗啡耐受大鼠脊髓背角 P2X4受体（P2X4R）的表达以及鞘内注射嘌呤受体拮抗剂TNP‐ATP（P2X1‐4R抑制剂）和 PPADS（P2X1‐3，5‐7 R 抑制剂）对慢性吗啡耐受大鼠的影响。【方法】60只成年雄性SD 大鼠，随机分为4组（ n ＝15）：对照组（C组）、吗啡组（M组）、吗啡＋ TNP‐ATP 组（T组）和吗啡＋ PPADS 组（P 组）。对照组：大鼠鞘内注射生理盐水（20μL）；M 组：大鼠鞘内注入吗啡10μg （10μL ）和生理盐水10μL ；T组：大鼠鞘内注入 TNP‐ATP 10 nmol（10μL ），半小时后注入吗啡10μg （10μL）；P 组：大鼠经鞘内置管并注入PPADS 10 nmol（10μL），半小时后注入吗啡10μg（10μL），2次／日，连续7 d 。每只大鼠于术前测定基础热痛阈，各组每次给药后测量大鼠热痛阈，d1、d3、d7最后一次测量痛阈后处死5只大鼠取脊髓背角，采用免疫组化检测 P2X4受体表达。【结果】M 组在 d1、d3的热痛阈显著高于 C 组（ P ＜0．05），随着吗啡注药天数增加，M 组热痛阈逐渐下降，d5、d7与 C 组的差异无统计学意义（ P ＞0．05）。与M组比较，P组各时点热痛阈无明显差异，但 T组热痛阈虽然也呈下降趋势，但明显缓于 M 组，T 组 d5、d7的热痛阈高于M组，差异有统计学意义（ P ＜0．05）。与 C 组比较，M组和P组在给药 d1、d3、d7大鼠脊髓背角 P2X4R表达上调（ P ＜0．05）。 鞘内注射 TNP‐ATP 组P2X4R表达明显低于M组和P组（ P ＜0．05）。 【结论】鞘内给予 TNP‐ATP 能够延缓大鼠慢性吗啡耐受的形成，其机制可能与其抑制P2X4R的表达有关。[Objective] To observe the changes of P2X4 receptor in spinal dorsal horn and explore the effect of TNP‐ATP （P2X1‐4 R inhibitor）and PPADS（P2X1‐3 ,5‐7 R inhibitor）intrathecally administered in chronic morphine tolerance rats .[Methods] A total of 60 male adult Sprague‐Dawley rats were randomly divided into four groups （ n = 15 each） of control ？ ,morphine （M） ;TNP‐ATP ＋ morphine （T） and PPADS ＋ morphine （P） .The animals received intrathecal injec‐tions of morphine 10 μg（10 μL）and saline 10 μL twice daily for 7 days （T1 - T7 ） in group M while an equal volume of sa‐line in group C .Groups T and P received intrathecal injections of 10 nmol（10 μL） TNP‐ATP and PPADS respectively for 7 days 30 min before the same treatment in group M .We assessed basic mechanical and thermal pain threshold at 2 days pre‐operation .Pain threshold to a thermal nociceptive stimulus was measured 30 min after dosing at T 1 - 7 in each group . Five rats in each group were sacrificed after last dosing at 1st ,3th ,7th days and spinal cord dorsal horn removed for de‐tecting the expression of P2X4 R by immunohistochemistry .[Results] Thermal pain threshold of group M was significant‐ly higher than that of group C at day 1 and 3 （ P 〈 0 .05） ,but decreased gradually afterwards with morphine dosing .And no significant difference existed between groups M and C at Day 5 and 7 （ P 〉 0 .05） .The difference was not significantly different between groups M and P （ P 〉 0 .05） .Thermal pain threshold of group T decreased more slowly than that of group M .Thermal pain threshold of group T was higher than that of group M ,especially during 5 and 7d （ P 〈 0 .05） .The expression of P2X4 R in groups M and P was obviously higher than that of group C at day 1 ,3 and 7 . The expression of P2X4 R significantly decreased in group T after an intrathecal dose of TNP‐ATP compared with groups M and P （ P 〈 0 .05） .[Conclusion] Intrathecal TNP‐ATP attenuates morphine

关 键 词：受体  嘌呤能P2 脊髓 吗啡 药物耐受性 

分 类 号：R971.2[医药卫生—药品]