国际麻醉学与复苏杂志   2023, Issue (8): 0-0
    
毛兰素对骨癌痛大鼠机械痛敏和热痛敏的影响
付翘楚, 时代, 田玉科1()
1.首都医科大学附属天坛医院
Erianin ameliorate mechanical allodynia and heat hyperalgesia induced by bone cancer in rat
 全文:
摘要:

目的 评价毛兰素(Erianin)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,应用随机数字表法分为5组(n=10):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)。通过右后肢胫骨骨髓腔注射10μL walker256乳腺癌细胞混悬液(约4×104个)的方法构建大鼠骨癌痛模型。于造模开始后第6d至21d,每天1次,腹腔注射Erianin和生理盐水。分别于术前1d、术后1、3、6、9、12、15、18和21d测定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天痛行为学评估结束后处死大鼠取脊髓组织,采用westem blot法和免疫荧光方法测定神经胶质纤维酸性蛋白(glial fibrillary acidic protein, GFAP)表达水平,酶联免疫吸附测定法检测脊髓促炎症细胞因子的含量变化。 结果 与Sham组相比,BCP组大鼠术后各时间点 PMWT和PWTL降低(p0.05);术后21d BCP组大鼠脊髓GFAP阳性细胞和蛋白表达增多,肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白细胞介素6 (interleukin 6, IL-6)、白细胞介素1β(Interleukin 1β, IL-1β)表达增多(p0.05)。与BCP+NS组相比,BCP+Erianin(L)、BCP+Erianin(H)组大鼠PMWT和PWTL均升高(P0.05),术后21d大鼠脊髓GFAP蛋白和TNF-α、IL-6、IL-1β含量均降低(p0.05)。 结论 Erianin可缓解大鼠骨癌痛,其机制可能与抑制脊髓星形胶质细胞活化减轻炎症反应有关。

关键词: 毛兰素;骨癌痛;星形细胞;炎性反应
Abstract:

Objective To evaluate the analgesic effect of Erianin on bone cancer pain(BCP) model and its effect on spinal astrocytes activation and inflammatory response. Methods Fifty female Sprague Dawley (SD) rats were randomly divided into five groups (10 rats for each group): Sham operation group (group Sham), bone cancer pain group (group BCP), BCP+natural saline group (group BCP+NS), BCP+low-dose Erianin group (group BCP+Erianin(L)), BCP+high-dose Erianin group (group BCP+Erianin(H)). Walker 256 rat mammary gland carcinoma cells (about 4×104celIs) 10μL was injected into the right tibia to mimic the clinic pathological process of BCP. The corresponding drugs and NS were injected intraperitoneally once a day from 6 d to 21d after surgery. Paw withdraw thermal latency (PWTL) and paw mechanical withdrawal threshold (PMWT) were measured 1d before and 1, 3, 6, 9, 12, 15, 18 and 21d after surgery. The animals were sacrificed on 21d after surgery and the spinal cord were collected, immunofluorescence and western blot were used to detect changes in glial fibril1ary acidic protein (GFAP) protein, enzyme-linked immunosorbent assay(ELISA) was used to detect the changes of proinflammatory cytokine expression. Results Compared with group Sham, group BCP showed remarkable decreases in PMWT and PWTL at each time points (p0.05), and marked increases of spinal astroglia cells and tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β) expression in spinal cord (p0.05). Compared with group BCP+NS, groups BCP+Erianin(L) and BCP+Erianin(H) showed remarkable increases in PMWT and PWTL (p0.05), and marked decreases of spinal astrocyte and TNF-α, IL-6, IL-1β expression in spinal cord (p0.05). Conclusion Erianin can alleviate BCP in rats,and the mechanism may be related to inhibiting activation of spinal astrocytes and attenuating inflammatory responses.

Key words: Erianin; bone cancer pain; astrocytes; inflammation