MPEP对吗啡耐受大鼠脊髓Ⅰ型IP3受体表达的影响

EFFECTS OF MPEP ON THE EXPRESSION OF IP3R-Ⅰ IN THE SPINAL CORD OF MORPHINE TOLERANT RATS

目的:探讨代谢型谷氨酸受体5(mGluR5)拮抗剂MPEP对吗啡耐受大鼠脊髓背角Ⅰ型IP3受体(IP3R-Ⅰ)表达的影响。方法:24只♂SD大鼠,随机分为4组:生理盐水对照组(NS)、吗啡耐受组、吗啡加MPEP组和MPEP组。通过测定大鼠甩尾潜伏期(TFL)评定各组大鼠的热痛阈变化。最后一次给药后次日取大鼠L4-5脊髓,Westernblot测定并比较各组脊髓背角IP3R-Ⅰ蛋白表达量。结果:吗啡组TFL呈下降趋势,但d7后与NS组比较无统计学意义(P>0.05)。吗啡加MPEP组TFL在用药后3-7 d与吗啡组比较差异有显著性(P<0.05)。吗啡组脊髓背角IP3R-Ⅰ表达较NS组升高(P<0.05),吗啡加MPEP组IP3R-Ⅰ的表达低于吗啡组(P<0.05),MPEP组IP3R-Ⅰ表达与NS组无统计学差异(P>0.05)。结论:鞘内重复注射吗啡后IP3R-Ⅰ表达上调。MPEP抑制吗啡耐受发展,机制可能与其抑制IP3R-Ⅰ表达有关。

Objective：To explore the effects of metabotropic glutamate receptor 5（mGluR5）antagonist MPEP on the expression of IP3 receptor subtype one（IP3R-I）in the spinal cord of morphine tolerant rats.Methods：Twenty four male Sprague-Dawley rats were randomly divided into four groups：NS control group,morphine tolerant group,morphine plus MPEP group and MPEP group.Tail flick latency（TFL） was measured before and 30 min after drug administration to assess thermal pain threshold of each group.The rats were killed on the day after last intrathecal administration and L4-5 segment of the spinal cord was removed for the determination of IP3R-I protein expression by Western blot method.Results：TFL of morphine tolerant group decreased gradually from d1 to d7,but no significant difference 7 days later compared with NS group（P〉0.05）.Morphine plus MPEP group had significant analgesic effect compared with morphine tolerant group from d3 to d7（P〈0.05）.The protein level of IP3R-I in morphine tolerant group was higher than that in NS group（P〈0.05）.The protein level in morphine plus MPEP group was lower than that in the morphine tolerant group（P〈0.05）.The expression of IP3R-I in MPEP group didn＇t change much compared with NS group（P〉0.05）.Conclusion：Expression of IP3R-I can upregulate after repeated administration of morphine intrathecally.MPEP can block the development of morphine tolerance,the mechanism of which is partly due to its inhibition effect on the expression of IP3R-I.