鞘内注射丹参酮ⅡA对骨癌痛小鼠痛行为及脊髓水平炎症因子的影响

目的探讨鞘内注射丹参酮ⅡA对骨癌痛小鼠热痛觉过敏及脊髓水平白介素-1β（IL-1β）、白介素-6（IL-6）、肿瘤坏死因子-理（TNF-仅）表达的影响。方法C3H／HeNCrlVr雄性小鼠84只，应用随机数字表法分为：（1）丹参酮IIA10μg组；（2）丹参酮IIA20μg组；（3）丹参酮IIA40μg组；（4）正常组；（5）DMSO＋Sham组；（6）丹参酮IIA＋Sham组；（7）DMSO＋Tumor组。用热辐射刺激仪测定缩足潜伏期（PWTL）。应用Real．timePCR技术检测mRNA表达。结果各组小鼠基础PⅥ吼差异无统计学意义（P〉0．05）。术后14d，与正常组相比，假手术组PwTL差异无统计学意义（P〉0．05），而骨癌痛组PWTL明显降低（P〈0．05）。术后21d，和正常组相比，丹参酮IIA＋Sham组、DMSO＋Sham组PwTL和脊髓IL-1β、IL-6、TNF-α表达差异均无统计学意义（P〉0．05）；DMSO＋Tumor组PWTL（6．19±1．26）s]明显低于正常组（16．01±1．59）s]（P〈0．05），脊髓IL—1β、IL-6、TNF—α表达则高于正常组；丹参酮IIA20μg组（9．83±1．26）s]、丹参酮IIA40μg组（10．29±2．95）s]PWTL高于DMSO＋Tumor组，脊髓IL-1β、IL-6、TNF-α表达则低于DMSO＋Tumor组（P〈0．05）；丹参酮IIA10μg组PwTL（6．67±0．96）S]、脊髓IL-1β、IL-6、TNF-α表达水平与DMSO＋Tumor组相比差异无统计学意义（P〉0．05）。结论鞘内注射丹参酮ⅡA具有剂量依赖性抗癌痛作用，抑制脊髓水平表达释放炎症因子IL-1β、IL-6、TNF-α可能是其机制之一。

The effect of intrathecal administration of Tanshinone IIA on bone cancer pain behavior and spinal expres-sion of inflammatory cytokines

Objective To investigate the effect of intrathecal injection of Tanshinone II A on bone cancer pain behavior and spinal IL-1 β, IL-6, TNF- α expression.Methods According to the random number table meth- od ,84 C3H/HeNCrlVr male mice were divided into： （1） Tanshinone IIA 10 μg group：the tumor mice were trea- ted by intrathecal administration （ once daily on the days 14-20 after inoculation of tumor cells） with Tanshinone IIA 10 μg; （2）Tanshinone IIA 20 μg group：the tumor mice were treated with Tanshinone IIA 20 μg; （3）Tanshi- none IIA 40 μg group：the tumor mice were treated with Tanshinone IIA 40 μg; （4） normal control group：the mice were given food and water ad libitum; （5） DMSO＋Sham group：the sham mice were treated with the same volume of 5%DMSO; （6） Tanshinone IIA＋Sham group：the sham mice were treated with Tanshinone IIA 40 μg; （7）DM- SO＋Tumor group：the tumor mice were treated with the same volume of 5%DMSO.The mice pain behaviors were as- sessed with the paw withdrawal thermal latency （PWTL） at the corresponding time points, then the mice were kill- ed and the samples of spinal cord were detected by real-time PCR.Results The basic values of PWTL had no sig- nificant differences among all groups （P〉0.05）. At day 14 after operation,no significant difference （P〉0.05） was found in the PWTL value between normal control group and the sham operation group. But in tumor group, the PWTL value was significantly lower than that of normal control group （P〈0.05）. At day 21 after operation, the PWTL and the level of spinal IL-1 β, IL-6, TNF-α expression had no significant differences （P〉0.05） among nor- mal control group,Tanshinone IIA＋Sham group and DMSO＋Sham group.The PWTL （（6.19±1.26）s） in DMSO＋ Tumor group was significantly lower than that of normal control group （ （ 16.01± 1.59 ） s ） （P〈 0.05 ）, but the level of IL-1β, IL-6, TNF-α expression was higher than that of normal control group. Compared with the normal group, the PWTL （ （9.83± 1.26）s;（10.29±2.95） s） of Tanshinone Ⅱ A 20 p~g and 40 p.g group was higher,and the level of spinal IL-1 β, IL-6, TNF-αexpression was lower （P〈0.05）.The PWTL and the levels of spinal IL-1 β, IL-6,TNF-α expression had no significant differences between Tanshinone IIA 10 μg group （ （ 6.67± 0.96 ） s ） and DMSO ＋ Tumor groun（P〉0.05）.Conclusinn lntrathecal iniaction of Tanshinone II A nlaw n role in anti-cnnear nain andinhibition of spinal inflammatory cytokine release may be one of its mechanisms.