丹酚酸C对大鼠骨癌痛的镇痛效应:脊髓星形胶质细胞和炎症反应在其中的作用  

Analgesic effect of salvianolic acid C on bone cancer pain in rats: the role of spinal astrocytes and inflammatory responses

作　　者：刘坤[1] 谢广伦 Liu Kun;Xie Guanglun(Department of Pain Management,First People′s Hospital of Shangqiu,Shangqiu 476100,China;Department of Pain Management,Cancer Hospital Affiliated to Zhengzhou University,Zhengzhou 450008,China)

机构地区：[1]河南省商丘市第一人民医院疼痛科,476100 [2]郑州大学附属肿瘤医院疼痛科,450008

出　　处：《中华麻醉学杂志》2019年第12期1476-1479,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价丹酚酸C对大鼠骨癌痛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级雌性SD大鼠30只,6周龄,体重180~200 g,采用随机数字表法分为3组(n=10):假手术组(S组)、骨癌痛组(BCP组)和丹酚酸C组(SalC组)。采用右侧胫骨骨髓腔注射乳腺癌Walker256细胞混悬液(约4×10^7个)10μl的方法,制备骨癌痛模型。S组注射等容量无菌磷酸盐缓冲液。于造模开始后第12至21天,SalC组腹腔注射1 mg/ml丹酚酸C溶液20 mg·kg^-1·d^-1,BCP组腹腔注射等容量生理盐水。于造模开始前1 d(T0)、造模开始后第3、6和9天(T1-3)、造模开始后第12、15、18和21天给药后6 h时(T4-7),测定机械缩足反应阈(MWT)和行走评分。于最后1次痛行为学评估结束后处死大鼠,取脊髓组织,采用Western blot法测定神经胶质纤维酸性蛋白(GFAP)表达水平,采用实时荧光定量PCR法测定GFAP、TNF-α、IL-6和IL-1β的mRNA表达水平。结果与S组比较,BCP组和SalC组T2-7时MWT降低,T3-7时行走评分降低,脊髓GFAP及其mRNA表达上调,TNF-α、IL-1β和IL-6的mRNA表达上调(P<0.05);与BCP组比较,SalC组T4-7时MWT升高,T5-7时行走评分升高,脊髓GFAP及其mRNA表达下调,TNF-α、IL-1β和IL-6的mRNA表达下调(P<0.05)。结论丹酚酸C可减轻大鼠骨癌痛,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。Objective To evaluate the analgesic effect of salvianolic acid C on bone cancer pain(BCP)and the role of spinal astrocytes and inflammatory responses in rats.Methods Thirty female Sprague-Dawley rats,weighing 180-200 g,were divided into 3 groups(n=10 each)using a random number table method:sham operation group(group S),group BCP and salvianolic acid C group(group SalC).BCP was induced by inoculating Walker 256 mammary gland caicinoma cell suspension(about 4×10^7 cells)10μl into the medullary cavity of the right tibia.The equal volume of sterile phosphate buffer solution was injected instead in group S.On 12-21 days after beginning of establishing the model,1 mg/ml SalC solution 20 mg·kg^-1·d^-1 were intraperitoneally injected in group SalC,while the equal volume of normal saline was injected in group BCP.The mechanical paw withdrawal threshold(MWT)and walking score were measured on 1 day before establishing the model(T0),on 3th,6th and 9th days after beginning of establishing the model(T1-3),and at 6 h after administration on 12th,15th,18th and 21st days after beginning of establishing the model(T4-7).The animals were sacrificed after the last measurement of pain threshold,and the L4-6 segments of the spinal cord were removed for determination of the expression of glial fibrillary acidic protein(GFAP)protein(by Western blot)and expression of GFAP,tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)and IL-1βmRNA(by fluorescent quantitative real-time polymerase chain reaction).Results Compared with group S,the MWT at T2-7 and walking score at T3-7 were significantly decreased,and the expression of GFAP protein and mRNA was up-regulated,and the expression of TNF-α,IL-6 and IL-1βmRNA was up-regulated in BCP and SalC groups(P<0.05).Compared with group BCP,the MWT at T4-7 and walking score at T5-7 were significantly increased,and the expression of GFAP protein and mRNA was down-regulated,and the expression of TNF-α,IL-6 and IL-1βmRNA was down-regulated in group SalC(P<0.05).Conclusion Salvianolic acid C can

关 键 词：丹参酚 疼痛 骨肿瘤 星形细胞 炎症 

分 类 号：R28[医药卫生—中药学]