毛兰素对骨癌痛大鼠机械痛敏和热痛敏的影响  

Erianin ameliorates mechanical allodynia and heat hyperalgesia induced by bone cancer in rat

作　　者：付翘楚 时代 田玉科[2] Fu Qiaochu;Shi Dai;Tian Yuke(Department of Anesthesiology,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Anesthesiology and Pain Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]首都医科大学附属北京天坛医院麻醉科,北京100070 [2]华中科技大学同济医学院附属同济医院麻醉疼痛研究所,武汉430030

出　　处：《国际麻醉学与复苏杂志》2023年第8期802-808,共7页International Journal of Anesthesiology and Resuscitation

基　　金：首都医科大学附属北京天坛医院青年基金(2017⁃YQN⁃05)。

摘　　要：目的评价毛兰素对骨癌痛(bone cancer pain,BCP)大鼠的镇痛效应及其与脊髓星形胶质细胞和炎症反应的关系。方法SPF级成年雌性SD大鼠50只,采用随机数字表法分为5组(每组10例):假手术组(Sham组)、骨癌痛组(BCP组)、骨癌痛+生理盐水组(BCP+NS组)、骨癌痛+毛兰素低剂量组[BCP+erianin(L)组]、骨癌痛+毛兰素高剂量组[BCP+erianin(H)组]。通过大鼠右后肢胫骨骨髓腔注射10μl Walker256乳腺癌细胞混悬液(约4×10^(4)个)的方法构建大鼠BCP模型,Sham组注射等体积煮沸灭活的乳腺癌细胞悬液。于造模开始后第6天至第21天,每天1次,BCP+erianin(L)组和BCP+erianin(H)组腹腔注射毛兰素,BCP+NS组腹腔注射生理盐水,Sham组和BCP组不进行腹腔注射。分别于术前1 d和术后1、3、6、9、12、15、18、21 d测定机械刺激缩足反射阈值(paw mechanical withdrawal threshold,PMWT)和热刺激缩足反射潜伏期(paw withdraw thermal latency,PWTL)。于术后21 d痛行为学评估结束后处死大鼠取胫骨和脊髓组织,H⁃E染色检测胫骨肿瘤细胞浸润情况,采用Western blot法和免疫荧光法测定脊髓星形胶质细胞特异性标记物神经胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)水平,ELISA法测定脊髓促炎症细胞因子(TNF⁃α、IL⁃6、IL⁃1β)水平变化。结果与Sham组比较:BCP组大鼠术侧胫骨H⁃E染色显示骨髓腔内充满肿瘤细胞,术侧后肢于术后6、9、12、15、18、21 d PMWT和PWTL降低(P<0.05),对侧后肢PMWT、PWTL差异无统计学意义(P>0.05);术后21 d BCP组大鼠脊髓GFAP水平和TNF⁃α、IL⁃6、IL⁃1β水平增加(P<0.05)。与BCP+NS组比较:BCP+erianin(L)组、BCP+erianin(H)组大鼠术侧后肢术后9、12、15、18、21 d PMWT和PWTL均升高(P<0.05),对侧后肢PMWT、PWTL差异无统计学意义(P>0.05);术后21 d大鼠脊髓GFAP和TNF⁃α、IL⁃6、IL⁃1β水平均降低(P<0.05)。与BCP+erianin(L)组比较:BCP+erianin(H)组大鼠术侧后肢术后12、15、18、21 d Objective To evaluate the analgesic effect of erianin on bone cancer pain(BCP)in rats and its relationship with spinal astrocytes and inflammatory response.Methods A total of 50 female Sprague Dawley(SD)rats were selected.According to the random number table method,they were divided into five groups(n=10):a Sham operation group(group Sham),a bone cancer pain group(group BCP),a BCP+normal saline group(group BCP+NS),a BCP+low⁃dose erianin group[group BCP+erianin(L)],a BCP+high⁃dose erianin group[group BCP+erianin(H)].A BCP model of rat was established through injection of 10μl Walker 256 breast cancer cells(about 4×10^(4) cells)into the right tibia.On days 6 to 21 after modeling,group BCP+erianin(L)and group BCP+Erinanin(H)were intraperitoneally injected with erinanin,and group sham was injected with equal volume boiled inactivated breast cancer cells suspension,once per day,group BCP+NS was intraperitoneally injected with normal saline,while no intraperitoneal injection was con⁃ducted in group Sham and group BCP.Then,the paw mechanical withdrawal threshold(PMWT)and paw withdraw thermal latency(PWTL)were measured 1 day before surgery and at postoperative 1,3,6,9,12,15,18 d and 21 d.On day 21 after surgery,the animals were sacrificed after behavior assessment and the tibia and spinal cord were collected.The infiltration of tumor cells in the tibia was de⁃tected by H⁃E staining.The expression of astrocyte specific marker,glial fibrillary acidic protein(GFAP)in spinal astrocytes were ex⁃amined by immunofluorescence and Western blot.The levels of proinflammatory cytokine,including tumor necrosis factor⁃α(TNF⁃α),interleukin 6(IL⁃6)and interleukin 1β(IL⁃1β),were detected by enzyme⁃linked immunosorbent assay(ELISA).Results Compared with group Sham,rats in group BCP presented the bone marrow cavity filled with tumor cells in the treated tibia by H⁃E staining,and re⁃markable decreases were observed in PMWT and PWTL at the treated side on postoperative 6,9,12,15,18 d and 21 d(P<0.05),whereas n

关 键 词：毛兰素 骨癌痛 星形细胞 炎症反应 

分 类 号：R965[医药卫生—药理学]