石蒜碱降低COX-2/NLRP3炎症信号缓解小鼠奥沙利铂化疗痛

Lycorine alleviates oxaliplatin-induced chemotherapy induced pain in mice via reducing COX-2/NLRP3 inflammatory signaling

目的探究石蒜碱对奥沙利铂化疗痛模型小鼠的作用及机制。方法40只小鼠随机分为4组,10只/组,分别为对照组、模型组、给药组和抑制剂组。采用连续5 d腹腔注射奥沙利铂的方法构建化疗痛模型;石蒜碱进行鞘内给药;检测各组小鼠行为学及炎症相关蛋白表达水平变化。结果与对照组相比,模型组小鼠自发缩足次数增加,机械痛阈值下降,运动距离及停留时间减少;脊髓组织中白细胞介素-1β(IL-1β)、胶质纤维酸性蛋白(GFAP)、环氧化酶2(COX-2)、NOD样受体蛋白3(NLRP3)和半胱氨酸蛋白酶-1(Caspase-1)表达水平均增加。与模型组相比,石蒜碱鞘内给药后小鼠自发缩足次数减少,机械痛阈值增加,运动距离及停留时间增加,结合COX-2并降低其表达,并下调IL-1β、GFAP、NLRP3和Caspase-1蛋白表达水平。结论石蒜碱抑制COX-2表达、阻断NLRP3炎症小体激活、降低脊髓炎症从而改善动物痛觉行为和运动能力。

Objective To explore the effect and mechanism of lycorine on oxaliplatin(OXA)induced chemotherapy pain in mice.Methods 40 mice were randomly divided into 4 groups,10 mice per group,which were respectively divided into control group,model group,administration group,and inhibitor group.A mouse model of chemotherapy induced pain was established by intraperitoneal injection of OXA for 5 consecutive days.Intrathecal administration of lycorine was performed.Behavioral changes and expression levels of inflammatory related proteins detected.Results Compared with control group,model group mice exhibited the increased number of spontaneous flinches,decreased mechanical nociceptive threshold,decreased movement distance and latency,and up-regulated expression levels of interleukin-1β(IL-1β),astrocytic marker glial fibrillary acidic protein(GFAP),cyclooxygenase-2(COX-2),NOD-like receptor protein 3(NLRP3),cysteinyl aspartate and specific proteinase 1(Caspase-1).Compared with model group,lycorine administration reduced the number of spontaneous flinches,increased mechanical nociceptive threshold,enhanced the movement distance and latency,bound and reduced COX-2 expression,down-regulated the expression levels of IL-1β,GFAP,NLRP3 and Caspase-1.Conclusion Lycorine reduces COX-2 expression,inhibits NLRP3 inflammasome activation,suppresses spinal inflammation,consequently alleviates pain behaviors and improved motor ability of mice.