鞘内注射大黄素纳米乳对骨癌痛大鼠的影响

The Effect of Intrathecal Injection of Emodin Nanoemulsion on Bone Cancer Pain in Rats

目的探讨大黄素纳米乳在大鼠骨癌痛模型中的镇痛效应。方法18只SD大鼠随机分为假手术组、模型组和大黄素组,每组6只。模型组和大黄素组均采用胫骨髓腔注射大鼠乳腺癌MRMT-1细胞建立骨癌痛模型,假手术组仅在胫骨髓腔内注射相同体积的Hank’s液。造模15d后,大黄素组单次鞘内注射5mg/mL大黄素纳米乳10μL,而模型组与假手术组注射相同体积生理盐水。采用X线、HE染色检测癌细胞对骨结构的破坏程度;“Up and Down”法观察不同时间点各组大鼠机械痛阈值变化;免疫荧光染色法测定大鼠脊髓胶质纤维酸性蛋白(GFAP)的表达变化;Western blot检测各组大鼠脊髓中GFAP蛋白表达。结果胫骨X线片显示术后模型组大鼠胫骨骨质损伤严重,HE染色显示骨髓腔有癌细胞浸润;与假手术组相比,术后7~14d模型组的机械痛阈值明显降低(P<0.05),大鼠脊髓中GFAP蛋白表达明显升高;与模型组相比,大黄素组在单次治疗后机械痛阈值出现明显升高(P<0.05),GFAP蛋白表达明显降低。结论大黄素纳米乳可降低星形胶质细胞过度激活,从而缓解大鼠骨癌痛。

Objective To investigate the analgesic effect of emodin nanoemulsion in rats with bone cancer pain model.Methods Eighteen SD rats were randomly divided into sham operation group,model group and emodin group,with 6 rats in each group.The model group and emodin group were injected with rat breast cancer MRMT-1 cells into the tibial medullary cavity to establish the bone cancer pain model.The sham operation group was only injected with the same volume of Hank's solution in the tibial medullary cavity.Fifteen days after modeling,10μL of 5 mg/mL emodin nanoemulsion was injected intrathecally in emodin group,while the same volume of normal saline was injected in model group and sham operation group.X-ray and HE staining were used to detect the damage degree of bone structure,which induced by cancer cells."Up and Down"method was used to observe the changes of mechanical pain threshold of rats at different time points in each group.The expressions of glial fibrillary acidic protein(GFAP)in spinal cord of rats in each group were detected by immunofluorescence staining and western blotting.Results X-ray images of rat tibia in the model group showed that the bone were severely damaged,and HE staining revealed cancer cell infiltration in the bone marrow cavity.Compared with the sham group,the mechanical pain threshold of rats in the model group was significantly decreased at 7-14 days after surgery(P<0.05),while the expressions of GFAP protein in the spinal cord of rats in the model group were significantly increased.Compared with the model group,the emodin group showed a significantly higher value of mechanical pain threshold after a single treatment(P<0.05),while the expressions of GFAP protein were significantly decreased.Conclusion Emodin nanoemulsion can reduce the overactivation of astrocytes to relieve the pain of bone cancer in rats.