慢性吗啡耐受大鼠脊髓谷氨酸转运体及谷氨酸的变化

目的：利用慢性关节炎吗啡耐受大鼠模型,观察脊髓背角谷氨酸转运体（GT）水平以及谷氨酸浓度的变化,阐述阿片耐受的机制。方法：24只SD大鼠随机分为四组（n=6）。吗啡组（M组）鞘内注入20μg吗啡,连续7 d;盐水对照组（S组）鞘内注入20μL生理盐水连续7 d;吗啡纳络酮组（MN组）鞘内注入20μg吗啡、10μg纳络酮连续7 d;纳络酮组（N组）鞘内注入10μg纳络酮连续7 d。于注药后第7 d观察大鼠的行为学变化,并取脊髓腰4~5节段,应用免疫组化法和计算机图像分析技术观察大鼠脊髓背角谷氨酸转运体（EAAT1,EAAT3）表达变化,采用毛细管电泳法检测谷氨酸浓度变化。结果：与S组、MN组、N组相比,M组大鼠脊髓背角谷氨酸转运体表达下降（P〈0.05）;缩脚潜伏期减少（P〈0.05）,谷氨酸浓度升高（P〉0.05）。上述变化在S组、MN组、N组之间没有差异（P〉0.05）。结论：形成关节炎吗啡耐受的大鼠脊髓背角EAAT1、EAAT3表达减少,谷氨酸浓度升高。

Alteration of Spinal Glutamate Transporter and Glutamate in Arthritis Rats with Morphine Tolerance

Objective To investigate the alteration of glutamate transporter and the glutamate in the dorsal horn of spinal cord after administration of morphine intrathecally and the mechanism of morphine tolerance in chronic inflamma- tion rat model. Method Twenty - four SD rats were randomly divided into 4 groups （ n = 6） ： morphine group （M group） with intrathecally administered 20μg morphine; Saline group （S group） with 20μl saline; morphine and naloxone group （MN group） with 20μg morphine and 10μg naloxone; naloxone group （N group） with 10μg naloxone. Seven days after administration of drugs, the behaviors＇test （paw withdrawal latency, PWL） was measured and lumbar4 -5 segment to the spinal cord was extracted to finish the immunohistochemistry and the concentration of glutamate measured by capil- lary electrophoresis （CE）. The computer image analysis system were used to observe the change of GT in the dorsal horn of the spinal cord. Results Compared with the S, MN, N groups expression of GT in the dorsal horn of the spinalcord the PWL were significantly reduced and the concentration of glutamate increased in the M group. Conclusion Chronic morphine administration can induce down - regulation of spinal glutamate transporters （EAATI, EAAT3） and elevation of the concentration of glutamate in the dorsal horn of the spinal cord under chronic inflammation.