骨通贴膏对甲醛疼痛模型大鼠的镇痛作用及机制研究
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摘要
目的:研究骨通贴膏对甲醛疼痛模型大鼠的镇痛作用及机制。方法:60只SD大鼠随机均分为空白组,模型组,骨通贴膏低、中、高剂量组(0.594、1.188、2.376 g/贴,含生药0.48、0.96、1.92 g)与醋酸泼尼松组(ig给药,0.005 4 g/kg,外贴基质),采用甲醛法复制大鼠疼痛模型,造模后立即给药。采用电子压痛仪测定给药1、2、3、4、6 h后各组大鼠痛阈值;给药6 h后,于腹主动脉取血0.3 m L并处死大鼠,采用酶联免疫吸附试验(ELISA)测定大鼠血浆中β-内啡肽(β-EP)、前列腺素E2(PGE2)含量,分光光度法测定大鼠血清、炎症组织中一氧化氮(NO)含量,放射免疫法检测大鼠血清、炎症组织及脑组织中P物质含量。结果:与造模前比较,模型组大鼠各个时段痛阈值均降低(P<0.05或P<0.01);与空白组比较,模型组大鼠PGE2、NO、炎症组织和脑组织中P物质含量显著升高(P<0.05或P<0.01);与模型组比较,骨通贴膏各剂量组大鼠给药后对应时间点的痛阈值升高,PGE2、炎症组织与脑组织中P物质含量降低(P<0.05或P<0.01),骨通贴膏中、高剂量组β-EP含量升高、炎症组织中NO含量降低(P<0.05或P<0.01),骨通贴膏高剂量组血清中NO含量降低(P<0.05)。结论:骨通贴膏具有一定的镇痛抗炎作用,其作用机制可能与降低PGE2、NO、P物质含量,升高β-EP含量有关。
OBJECTIVE:To study the analgesic effect and mechanism of Gutongtie paste on model rats with formaldehyde-induced pain. METHODS:60 SD rats were randomly divided into blank group,model group,Gutongtie paste low-dose,mediumdose,high-dose groups(0.594,1.188. 2.376 g/paste,containing crude drug 0.48,0.96,1.92 g)and prednisone acetate group(ig,0.005 4 g/kg,external bonding matrix). Model rats with pain was induced by formaldehyde method and immediately administrated after modeling. Electronic tenderness instrument was adopted to determine the pain threshold of rats' ankle joint after administration of 1,2,3,4,6 h. After 6 h,blood sample 0.3 m L was taken from abdominal aorta then rats were sacrificed. Enzyme linked immunosorbent assay(ELISA)was conducted to determine the β-endorphin(β-EP),prostaglandin E2(PGE2)contents;spectrophotometry was used to determine nitric oxide(NO)content in rats' serum and inflammatory tissue;and radioimmunoassay was adopted to detect the substance P content in rats' serum,inflammatory tissue and brain tissue. RESULTS:Compared with before modeling,pain thresholds in model group at each period were significantly decreased(P<0.05 or P<0.01). Compared with blank group,PGE2,NO of rats,substance P content in inflammatory tissue and brain tissue in model group were significantly increased(P<0.05 or P<0.01). Compared with model group,pain thresholds in Gutongtie paste groups at corresponding time points were increased,PGE2 and substance P contents in inflammatory tissue and brain tissue were decreased(P<0.05 or P<0.01);β-EP and NO contents in serum in Gutongtie paste medium-dose,high-dose groups(P<0.05 or P<0.01),NO contents in serum in Gutongtie paste high-dose group were decreased(P<0.05). CONCLUSIONS:Gutongtie paste has a certain analgesic and anti-inflammatory effect, and the mechanism may be related to reducing PGE2,NO,substance P contents,increasing β-EP content.
OBJECTIVE:To study the analgesic effect and mechanism of Gutongtie paste on model rats with formaldehyde-induced pain. METHODS:60 SD rats were randomly divided into blank group,model group,Gutongtie paste low-dose,mediumdose,high-dose groups(0.594,1.188. 2.376 g/paste,containing crude drug 0.48,0.96,1.92 g)and prednisone acetate group(ig,0.005 4 g/kg,external bonding matrix). Model rats with pain was induced by formaldehyde method and immediately administrated after modeling. Electronic tenderness instrument was adopted to determine the pain threshold of rats' ankle joint after administration of 1,2,3,4,6 h. After 6 h,blood sample 0.3 m L was taken from abdominal aorta then rats were sacrificed. Enzyme linked immunosorbent assay(ELISA)was conducted to determine the β-endorphin(β-EP),prostaglandin E2(PGE2)contents;spectrophotometry was used to determine nitric oxide(NO)content in rats' serum and inflammatory tissue;and radioimmunoassay was adopted to detect the substance P content in rats' serum,inflammatory tissue and brain tissue. RESULTS:Compared with before modeling,pain thresholds in model group at each period were significantly decreased(P<0.05 or P<0.01). Compared with blank group,PGE2,NO of rats,substance P content in inflammatory tissue and brain tissue in model group were significantly increased(P<0.05 or P<0.01). Compared with model group,pain thresholds in Gutongtie paste groups at corresponding time points were increased,PGE2 and substance P contents in inflammatory tissue and brain tissue were decreased(P<0.05 or P<0.01);β-EP and NO contents in serum in Gutongtie paste medium-dose,high-dose groups(P<0.05 or P<0.01),NO contents in serum in Gutongtie paste high-dose group were decreased(P<0.05). CONCLUSIONS:Gutongtie paste has a certain analgesic and anti-inflammatory effect, and the mechanism may be related to reducing PGE2,NO,substance P contents,increasing β-EP content.
引文
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[2]王冠.骨通贴膏对急性软组织损伤患者疼痛的影响[J].中国医药导刊,2015,17(12):1239-1241.
[3]王涛然,刘群.天和骨通贴膏配合手法治疗骶髂关节痛100例[J].中国医药导刊,2015,17(8):826-827、834.
[4]陈荣明,姜淼,殷书梅,等.复方南星止痛膏对甲醛等致炎症疼痛模型大鼠止痛作用及c-fos表达的影响[J].世界中西医结合杂志,2008,3(8):454-456.
[5]胡晨,陈荣明,殷书梅,等.复方南星止痛膏的镇痛作用观察及机理探讨[J].南京中医药大学学报,2009,25(2):140-142.
[6]李仪奎.中药药理实验方法学[M].2版.上海:上海科学技术出版社,2006:246.
[7]孙悦,丁成华,丁明,等.《素问·举痛论》病因病机与诊治发微[J].世界中医药,2014(3):302-304.
[8]杜冠峰,何宇愿,谌江城,等.中药镇痛活性成分经皮给药研究进展[J].安徽医药,2015,19(1):1-5.
[9]杜婕莹,曾森,王璐,等.聚异丁烯骨通贴膏经皮肤给药的安全性研究[J].中国药房,2016,27(25):3512-3514.
[10]张梦,骆艳丽.疼痛相关疾病动物模型研究概况[J].西部医学,2014,26(6):814-816.
[11]Fischer M,Carli G,Raboisson P,et al.The interphase of the formalin test[J].Pain,2014,155(3):511-521.
[12]沈立姿,房立丛,于津鹏,等.大鼠疼痛模型研究进展[J].重庆医学,2013,42(10):1166-1169.
[13]王晓玲,乐健,洪战英,等.中药镇痛实验的研究进展[J].药学服务与研究,2011,11(3):213-217.
[14]陆怡,朱元章,朱国福,等.中药镇痛机理研究概述[J].世界中医药,2015(4):629-632.