首页|骨痛灵方对骨癌痛模型小鼠脊髓小胶质细胞及炎症因子的影响

骨痛灵方对骨癌痛模型小鼠脊髓小胶质细胞及炎症因子的影响

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目的 观察骨痛灵方对骨癌痛模型小鼠脊髓小胶质细胞及炎症因子的影响.方法 将50 只C57BL/6 小鼠按照随机数字表法分为 5 组,假手术组、模型组及骨痛灵方低、中、高剂量组,各 10 只.假手术组予磷酸盐缓冲液(PBS)溶液胫骨骨髓腔注射,余4 组予Lewis肺癌细胞悬液胫骨骨髓腔注射造模,造模后第 7 天给药.骨痛灵方低、中、高剂量组分别予骨痛灵水煎剂溶液0.4、0.8、1.6 g/mL,每次 9 mL/kg灌胃;假手术组、模型组均予 0.9%氯化钠注射液9 mL/kg灌胃.连续给药14 天.比较各组小鼠热痛觉缩足潜伏期(PWTL);比较各组小鼠左侧腰段脊髓背角小胶质细胞标志物钙结合蛋白(Iba-1)表达;比较各组小鼠脊髓CC趋化因子配体-20(CCL20)、白细胞介素 6(IL-6)、IL-10 表达.结果 治疗前、给药7 天、给药14 天,假手术组PWTL比较差异均无统计学意义(P<0.05),模型组及骨痛灵方低、中、高剂量组PWTL均逐渐降低(P<0.05);与假手术组同期比较,模型组PWTL均降低(P<0.05);治疗前,模型组和骨痛灵方低、中、高剂量组PWTL两两比较差异均无统计学意义(P>0.05);与模型组给药同期比较,骨痛灵方低、中、高剂量组PWTL均升高(P<0.05);与骨痛灵方低剂量组给药同期比较,骨痛灵方中、高剂量组PWTL均升高(P<0.05);骨痛灵方中、高剂量组PWTL比较差异无统计学意义(P>0.05).与假手术组比较,模型组小鼠Iba-1 阳性面积增加(P<0.05);与模型组比较,骨痛灵方低、中、高剂量组小鼠Iba-1 阳性面积降低(P<0.05);与骨痛灵方低剂量组比较,骨痛灵方中、高剂量组小鼠Iba-1 阳性面积降低(P<0.05);骨痛灵方中、高剂量组小鼠Iba-1 阳性面积比较差异无统计学意义(P>0.05).与假手术组比较,模型组小鼠脊髓 CCL20、IL-6 表达均升高(P<0.05),IL-10 表达降低(P<0.05);与模型组比较,骨痛灵方低、中、高剂量组小鼠脊髓CCL20、IL-6 表达均降低(P<0.05),IL-10 表达升高(P<0.05);与骨痛灵方低剂量组比较,骨痛灵方中、高剂量组小鼠脊髓CCL20、IL-6 表达降低(P<0.05),IL-10 表达升高(P<0.05);骨痛灵方中、高剂量组CCL20、IL-6、IL-10 表达比较差异无统计学意义(P>0.05).结论 骨痛灵方可能通过抑制脊髓小胶质细胞的活化及相关炎症因子的表达发挥镇痛作用.
Effects of Gutongling Formula on spinal microglia and inflammatory factor in model mice with bone cancer pain
Objective To investigate the effects of Gutongling Formula on spinal microglia and inflammatory factor in model mice with bone cancer pain(BCP).Methods Fifty C57BL/6 mice were randomly assigned into sham operation group(SG),model group(MG),and Gutongling Formula groups(low does group[C1G],medium does group[C2G]and high dose group[C3G]),with 10 mice in each group.Mice in SG and other groups received injection of phosphate buffer solution(PBS)and Lewis lung cancer cell suspension in tibial medullary cavity for modeling respectively.Administration was performed on the 7th day after modeling.The mice in the Gutongling Formula groups were given 0.4 g/mL,0.8 g/mL and 1.6 g/mL Gutongling Decoction by gavage(9 ml·kg-1)respectively once a day.The mice in SG and MG were given the same dose of normal saline by gavage once a day.A 14-day administration was performed to compare paw withdrawal thermal latency(PWTL),microglial marker ionized calcium binding adaptor molecule-1(Iba-1)in the left lumbar segment of spinal dorsal horns,C-C motif chemokine ligand 20(CCL20),interleukine-6(IL-6),IL-10.Results On day 0 and on days 7 and 14,none of the PWTL differed significantly in SG(P>0.05),PWTL of other groups gradually decreased(P<0.05),and the pain gradually worsened.The PWTL in MG was significantly lower than synchronous that of SG(P<0.05).The difference was not statistically significant in PWTL before treatment between MG and Gutongling Formula groups(P>0.05).The PWTL in Gutongling Formula groups was significantly higher than synchronous that of MG.The PWTL in C2G and C3G was significantly higher than synchro-nous that of C1G(P<0.05).The PWTL was comparable between C2G and C3G(P>0.05).The Iba-1 positive area in MG was significantly higher than that of SG(P<0.05),which in C1G,C2G and C3G were significantly lower thanthose in MG(P<0.05),and C1G was significantly lower than MG(P<0.05).The Iba-1 positive area was comparable between C2G and C3G(P>0.05).Compared with SG,MG presented significantly increased CCL20 and IL-6 expression(P<0.05),and sig-nificantly decreased IL-10 expression(P<0.05).Compared with MG,the Gutongling Formula groups presented significantly decreased CCL20 and IL-6 expression(P<0.05),and significantly increased IL-10 expression(P<0.05).Compared with C1G,C2G and C3G presented significantly decreased CCL20 and IL-6 expression(P<0.05),and significantly increased IL-10 expression(P<0.05).Theexpression of CCL20,IL-6 and IL-10 was comparable between C2G and C3G(P>0.05).Conclusion Gutongling Formula may exert an analgesic effect by inhibiting the activation of spinal microglia and the expression of inflammatory factor.

Bone cancerPainAnimal experimentTraditional Chinese medicine therapy

罗琴琴、严叶香、郭锋健、鲁叶云

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湖北省武汉市中西医结合医院中医科,湖北 武汉 430000

上海市第十人民医院崇明分院中医科,上海 202150

骨肿瘤 疼痛 动物实验 中药疗法

国家自然科学基金项目湖北省科学技术厅2020年省科技计划项目(第一批)

823053462020CFB359

2024

河北中医
河北省医学情报研究所,河北省中医药学会

河北中医

CSTPCD
影响因子:0.951
ISSN:1002-2619
年,卷(期):2024.46(6)