目的评价鞘内注射曲马多对大鼠细胞免疫功能的影响。方法32只成年雄性SD大鼠,体重250.300g,采用改良Yaksh法进行鞘内置管成功后,随机分为4组(n=8):生理盐水组(NS组);不同剂量曲马多组(T1-3组)分别鞘内输注曲马多50、25、12.5μg/h。置管后5d鞘内输注生理盐水或不同剂量曲马多,泵容量200m,泵速1μl/h,鞘内输注7d后行福尔马林实验,采用痛级评分评价镇痛效果后处死大鼠,称取体重及脾脏重量,计算脾脏指数,并分离、培养脾脏淋巴细胞,甲基-^3H胸腺嘧啶核苷掺入法检测脾脏T淋巴细胞增殖转化水平,乳酸脱氢酶释放法检测脾脏自然杀伤(NK)细胞活力。结果与NS组比较,不同剂量曲马多组在福尔马林给药后5min和20~60min时痛级评分降低,T1组脾脏指数、T淋巴细胞增殖转化水平降低(P〈0.05),T2组和T3组脾脏指数和T淋巴细胞增殖转化水平差异无统计学意义(P〉0.05)。不同剂量曲马多组NK细胞活力与NS组比较差异无统计学意义(P〉0.05)。结论大鼠鞘内注射曲马多在产生良好的抗伤害作用时,曲马多12.5、25μg/h不抑制细胞免疫功能,较大剂量(50μg/h)抑制细胞免疫功能。
Objective To evaluate the effects of intrathecal (IT) tramadol on cell-mediated immunity in rats. Methods Thirty-two SD rats weighing 250-300 g were randomly divided into 4 groups ( n = 8 each) : control group (C) and 3 tramadol groups (T1, T2, T3 ) . The animals were anesthetized with intraperitoneal chloral hydrate 300-350 mg/kg. Micro-catheter was inserted into the subarachnoid space at the lumbar region according to modified Yaksh technique. Correct implantation of the spinal catheter was confirmed by aspiration of cerebral-spinal fluid (CSF). In the 3 tramadol groups (T1 , T2, T3 ), tramadol was continuously infused through spinal catheter at 50, 25 and 12.5 μg/h respectively for 7 days starting from the 5 th day after IT catheter implantation. In control group normal saline was continuously infused instead of tramadol. On the 7 th day of IT tramadol infusion 5 % formalin 50 was injected subcutaneously into the plantar surface of the left hindpaw. The number of flinches, lickings and total time of licking were recorded for 60 min. Pain intensity scores (PIS) (0 = no pain, 3 = severe pain) were recorded to assess the antinociceptive effects of IT tramadol. The animals were killed after evaluation of pain intensity. Body weight and spleen weight were measured. Spleen index (spleen weight/body weight) was calculated. T-lymphocyte function was evaluated based on Concanavalin A (ConA)-induced splenocyte proliferation. A modified lactic acid dehydrogenase (LDH) release assay was used to assess NK cell activity. Results The PISs were significantly lower in group T1 , T2 and T3 than in control group. The spleen index and spleenocyte proliferation induced by ConA were significantly suppressed in group T1 , but there was no significant difference between control group and group T2 and T3. There was no significant difference in NK cell activity between the control group and the 3 tramadol groups. Conclusion IT tramadol has significant antinociceptive effect. Tramadol 50μ