鞘内注射脂氧素A4对切口疼痛大鼠的抗伤害性感受作用

The antinociceptive effect of aspirin-triggered lipoxin administered by intrathecal in a rat model of incision pain

目的观察脊髓水平阿司匹林诱生型脂氧素A4(ATL)对切口疼痛大鼠热痛敏、机械痛敏的影响,探讨其是否具有抗伤害性感受作用及其作用机制。方法雄性SD大鼠72只制作动物切口疼痛模型,随机分为4组:生理盐水组(NS组),ATL组,脂氧素受体激动剂组(BML-111组),脂氧素受体拮抗剂组(BOC-2组),每组18只,于手术前(T0),术后2 h(T2)、4 h(T4)、6 h(T6)、8 h(T8)、10 h(T10)通过热板实验、探针刺激实验评估对大鼠热痛敏、机械痛敏的影响。实时PCR检测脊髓炎症因子(TNF-α、IL-6)m RNA的表达,Western blot检测腰段椎体p-ERK的表达。结果组内与T0比较发现,四组切口疼痛模型后2 h,大鼠TWL、MWT均减少(P<0.05),ATL和BML-111组内T4、T6、T8、T10与T2比较,TWL、MWT均增加(P<0.05),NS和Boc-2组内T4、T6、T8、T10与T2比较,TWL、MWT无明显变化。ATL和BML-111两组与NS组组间比较,T4、T6、T8、T10的TWL、MWT均增加(P<0.05)。RT-PCR显示,与NS组、Boc-2组比较,ATL组和BML-111组TNF-α、IL-6脊髓m RNA表达明显减少(P<0.05);Western blot结果显示,与NS组、Boc组相比,ATL组、BML-111组p-ERK蛋白表达降低;Boc组与NS组表达无差异。结论切口模型术后后足出现热缩足潜伏期缩短、机械缩足反应阈值减低,鞘内注射阿司匹林诱生型脂氧素A4可以减轻痛觉过敏,降低脊髓背角神经元中促炎症因子的表达,抑制脊髓p-ERK的表达。

Objective To investigated whether aspirin-triggered lipoxin （ATL） could decrease thermal withdrawal latency （TWL） and mechanical withdrawal threshold （MWT） administered by intrathecal in a rat model of incision pain and the mechanism. Methods Seventy-two male Sprague-Dawley rats were randomly allocated into 4 groups （n=18/group）： NS group, ATL group, BML-111 Group and Boc-2 group. All the SD rats were implanted with a catheter intrathecally. The effect of intrathecal administration of all drugs on therma land mechanical threshold were evaluated by hot plate and Frey filaments experiment from preoperation to the postoperative 2nd hour, 6th hour, 8th hour and 10th hour. The expressed of TNF-αand IL-6 mRNA will be assessed by Real-time PCR. Western blot will be carried out for the protein level of phosphorylated extracellular signal-regulated kinase （p-ERK）. Results Compared with baseline, the values of TWL and MWT were significantly lower in all groups, but increased at T4, T6, T8, T10 compared with T2 in ATL group and BML-111 group, nor in NS group and Boc-2 group. A comparison of NS group, Boc-2 group and ATL group, BML-111 group indicated that the expression of TNF-αand IL-6 mRNA decreased in the latter two groups. The expressed protein level of ERK showed a marked decrease in ATL and BML-111 group by Western blot, no significant difference existed between NS group and Boc-2 group. Conclusions Aspirin-triggered lipoxin （ATL） elicited antinociceptive effect by decreasing thermal withdrawal latency （TWL） and mechanical withdrawal threshold （MWT） and attenuating the expressed of TNF-α and IL-6 mRNA and protein level of p-ERK administered by intrathecal in a rat model of incision pain.