元胡止痛滴丸对痛经模型大鼠的镇痛作用及机制研究
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摘要
目的观察元胡止痛滴丸对痛经模型大鼠的镇痛作用,并探讨其可能的作用机制。方法选取雌性SPF级Wistar大鼠60只,按照体重随机区组的方法将其分为对照组,模型组,元胡止痛滴丸小(0.2 g生药/kg)、低(0.4 g生药/kg)、中(0.8 g生药/kg)、高(1.6 g生药/kg)剂量组,每组各10只。腹腔注射缩宫素致痛诱发大鼠形成痛经模型,腹腔注射苯甲酸雌二醇致敏后连续灌胃给药3 d,观察元胡止痛滴丸对痛经引起的扭体反应的潜伏期和扭体次数的影响,并检测血浆中前列腺素F_(2α)、前列腺素E_2等与疼痛相关因子的水平。结果与模型组比较,元胡止痛滴丸低、中、高剂量组大鼠的扭体次数明显减少(P <0.05或P <0.01),扭体潜伏期有延长趋势,但由于个体差异导致标准差较大,差异无统计学意义(P> 0.05)。与模型组比较,元胡止痛滴丸中、高剂量组大鼠血浆中β内啡肽及前列腺素E_2含量显著升高(P <0.05或P <0.01),去甲肾上腺素、5羟色胺及前列腺素F_(2α)/前列腺素E_2比值显著降低(P <0.05或P <0.01),元胡止痛滴丸高剂量组大鼠前列腺素F2α含量明显降低(P <0.05);元胡止痛滴丸中、高剂量组大鼠血浆中血栓素B_2、6-酮前列腺素F_(1α)含量与模型组比较差异无统计学意义(P> 0.05)。结论元胡止痛滴丸在0.8～1.6 g生药/kg剂量下对痛经模型大鼠具有显著的镇痛作用,改善外周血中与疼痛相关的前列腺素、单胺类递质及β-内啡肽水平是其发挥多途径镇痛作用的可能机制。
Objective To study the analgesic effect of Yuanhu Zhitong Dropping Pills on dysmenorrhea model rats and to discuss the possible mechanism.Methods Sixty female SPF grade Wistar rats were divided into control group,model group,small-dose(0.2 g crude drug/kg),low-dose(0.4 g crude drug/kg),medium-dose(0.8 g crude drug/kg),high-dose(1.6 g crude drug/kg)of Yuanhu Zhitong Dropping Pills group according to weight random block method,with 10 rats in each group.The model of dysmenorrhea was induced by intraperitoneal injection of oxytocin,and Yuanhu Zhitong Dropping Pills was administered by intragastric administration for 3 days after sensitized by intraperitoneal injection of estradiol benzoate.The effect of Yuanhu Zhitong Dropping Pills was observed by detecting latency stage and times of writhing response induced by dysmenorrhea,and the level of factors related to pain such as prostaglandin F_(2α) and prostaglandin E_2 in plasma were also detected.Results Compared with model group,the times of writhing response in low-dose,medium-dose,high-dose of Yuanhu Zhitong Dropping Pills group significantly decreased(P<0.05 or P<0.01),and the preclinical period of writhing response in low-dose,medium-dose,high-dose of Yuanhu Zhitong Dropping Pills group showed an extension trend,while the standard deviation was large due to individual differences,the differences were not statistically significant(P>0.05).Compared with model group,the level of β-endorphin and prostaglandin E_2 in medium-dose and high-dose of Yuanhu Zhitong Dropping Pills group increased significantly(P<0.05 or P<0.01),and the level of noradrenaline,5-hydroxytryptamine,the ratio of prostaglandinprosta-glandinsignificantly(P<0.05 or P<0.01),the level of prostaglandinhigh-dose of Yuanhu Zhitong Dropping Pills group decreased significantly(P<0.05).There was no statistically significant difference on the level of thromboxane6-Keto-prostaglandinmedium-dose,high-dose of Yuanhu Zhitong Dropping Pills group and model group(P>0.05).Conclusion Yuanhu Zhitong Dropping Pills has significant analgesic effect on dysmenorrhea model rats with the dose of 0.8-1.6 g crude drug/kg.The multi-way analgesic effect is probably related to improved levels of pain-associated prostaglandins,monoamine transmitters,andβ-endorphin in peripheral blood.
Objective To study the analgesic effect of Yuanhu Zhitong Dropping Pills on dysmenorrhea model rats and to discuss the possible mechanism.Methods Sixty female SPF grade Wistar rats were divided into control group,model group,small-dose(0.2 g crude drug/kg),low-dose(0.4 g crude drug/kg),medium-dose(0.8 g crude drug/kg),high-dose(1.6 g crude drug/kg)of Yuanhu Zhitong Dropping Pills group according to weight random block method,with 10 rats in each group.The model of dysmenorrhea was induced by intraperitoneal injection of oxytocin,and Yuanhu Zhitong Dropping Pills was administered by intragastric administration for 3 days after sensitized by intraperitoneal injection of estradiol benzoate.The effect of Yuanhu Zhitong Dropping Pills was observed by detecting latency stage and times of writhing response induced by dysmenorrhea,and the level of factors related to pain such as prostaglandin F_(2α) and prostaglandin E_2 in plasma were also detected.Results Compared with model group,the times of writhing response in low-dose,medium-dose,high-dose of Yuanhu Zhitong Dropping Pills group significantly decreased(P<0.05 or P<0.01),and the preclinical period of writhing response in low-dose,medium-dose,high-dose of Yuanhu Zhitong Dropping Pills group showed an extension trend,while the standard deviation was large due to individual differences,the differences were not statistically significant(P>0.05).Compared with model group,the level of β-endorphin and prostaglandin E_2 in medium-dose and high-dose of Yuanhu Zhitong Dropping Pills group increased significantly(P<0.05 or P<0.01),and the level of noradrenaline,5-hydroxytryptamine,the ratio of prostaglandinprosta-glandinsignificantly(P<0.05 or P<0.01),the level of prostaglandinhigh-dose of Yuanhu Zhitong Dropping Pills group decreased significantly(P<0.05).There was no statistically significant difference on the level of thromboxane6-Keto-prostaglandinmedium-dose,high-dose of Yuanhu Zhitong Dropping Pills group and model group(P>0.05).Conclusion Yuanhu Zhitong Dropping Pills has significant analgesic effect on dysmenorrhea model rats with the dose of 0.8-1.6 g crude drug/kg.The multi-way analgesic effect is probably related to improved levels of pain-associated prostaglandins,monoamine transmitters,andβ-endorphin in peripheral blood.
引文
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[4]嵇波,张露芬,朱江,等.痛经模型建立和评价方法的思考[J].中国药理学通报,2008,24(6):711-714.
[5]孙文萍,王树林,李永平.电针对原发性痛经模型大鼠镇痛作用的实验研究[J].青海医药杂志,2017,47(10):1-3.
[6]黄诗敏,陈思达,龙泳伶,等.腹针治疗痛经研究的系统评价[J].现代医院,2016,16(12):1724-1730.
[7]李冠仪.电针关元、三阴交对痛经模型大鼠的镇痛作用及机制研究[D].广州:广州中医药大学,2015:1-47.
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[12]李倩,谢萍,白春霞,等.复方金铃四逆四物失笑散治疗实验性原发性痛经的作用机制研究[J].中国中西医结合杂志,2016,36(9):1087-1090.
[13]张福云,王文华,陈琳,等.暖宫七味散对原发性痛经寒凝血滞证患者血清PGF2α、PGE2水平及子宫微循环的影响[J].中国现代医生,2017,55(23):10-12,16.
[14] Liedman R,Hansson SR,Howe D,et al. Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects[J]. Gynecol Endocrinol,2008,24(9):508-513.
[15] Shangold MM,Aksel S,Schomberg DW,et al. Plasma prostaglandin F2-alpha levels in dysmenorrehic women[J].Fertil Steril,1976,27(10):1171-1175.
[16]齐丹丹,张玲,申松希,等.不同针刺刺激量对寒凝证类痛经模型大鼠扭体反应及子宫内前列腺素物质含量的影响[J].中医药信息,2015,32(4):48-51.
[17]贾小红,巩海亮,宋兰英,等.针刺治疗对原发性痛经患者性激素及前列腺素分泌的调节作用[J].中国医药导报,2016,13(7):76-79.
[18]崔静宜.复方金铃四逆四物失笑散对原发性痛经大鼠模型的作用机制[D].成都:成都中医药大学,2016:1-41.
[19]方玲,朱新冰,尹菊,等.经前三剂止痛方治疗实验性痛经模型大鼠作用机制研究[J].天津中医药,2010,27(1):46-49.
[20]庄惠琴.疏肝化瘀汤治疗气滞血瘀型原发性痛经的临床疗效观察[J].中国当代医药,2016,23(12):119-121.
[21]陆煜,马瑞芬,钱黎.温针灸治疗原发性痛经的临床效果与安全性评价[J].中国现代医生,2018,56(8):134-136,140.
[22]秦丽娟,卫红霞,郭述真.β-内啡肽与女性生殖内分泌[J].山西医科大学学报,2007,38(4):361-364.
[23]宋卓敏,屈彩芹,张远,等.痛经宁颗粒对痛经大鼠中枢及外周β-EP含量的影响[J].天津中医药,2004,21(5):405-407.
[24]周杰,陈贞羽,龚杰,等.不同参数组合电针对SNL大鼠镇痛效应观察及对下丘脑内啡肽的影响[J].中国医药导报,2017,14(23):18-21.
[25]刘群,黄欣,苏乐群.元胡白芷配方对大鼠外周血中致痛和镇痛物质的影响[J].中国医院药学杂志,2012,32(8):593-596.
[26]韩彦琪,许浚,张喜民,等.基于网络药理学的元胡止痛滴丸治疗原发性痛经的作用机制研究[J].药学学报,2016,51(3):380-387.
[27]张新庄,柯志鹏,李娜,等.从网络角度研究元胡止痛胶囊治疗头痛与痛经的分子作用机制[J].中国新药杂志,2016,25(20):2323-2330.
[28]段英丹,杨璐,柴程芝,等.麻黄中的主要活性成分对原发性痛经模型小鼠的作用研究[J].世界中西医结合杂志,2018,13(3):344-347,352.
[29]齐丹丹,张梅,郭孟玮,等.不同针刺刺激量对寒凝证类痛经模型大鼠血清及子宫组织内钙离子的影响[J].中医药导报,2015,21(7):1-5.
[2]李思思,许浚,张铁军,等.HPLC法同时测定元胡止痛滴丸中6种成分[J].中草药,2015,46(21):3198-3201.
[3]韩彦琪,许浚,龚苏晓,等.HPLC-QTOF/MS方法分析元胡止痛方的化学成分[J].药学学报,2017,52(1):132-138.
[4]嵇波,张露芬,朱江,等.痛经模型建立和评价方法的思考[J].中国药理学通报,2008,24(6):711-714.
[5]孙文萍,王树林,李永平.电针对原发性痛经模型大鼠镇痛作用的实验研究[J].青海医药杂志,2017,47(10):1-3.
[6]黄诗敏,陈思达,龙泳伶,等.腹针治疗痛经研究的系统评价[J].现代医院,2016,16(12):1724-1730.
[7]李冠仪.电针关元、三阴交对痛经模型大鼠的镇痛作用及机制研究[D].广州:广州中医药大学,2015:1-47.
[8]王得志,谢琳,王立军,等.推拿治疗原发性痛经的研究进展[J].医学综述,2018,24(2):367-370,377.
[9]陈俏花,王薇华.青春期少女痛经中医体质类型的临床研究及分析[J].中国当代医药,2017,24(7):173-175.
[10] Valentin L,Sladkevicius P,Kindahl H,et al. Effects of a vasopressin antagonist in women with dysmenorrhea[J].Gynecol Obstet Invest,2000,50(3):170-177.
[11]华永庆,洪敏,朱荃.原发性痛经研究进展[J].南京中医药大学学报,2003,19(1):62-64.
[12]李倩,谢萍,白春霞,等.复方金铃四逆四物失笑散治疗实验性原发性痛经的作用机制研究[J].中国中西医结合杂志,2016,36(9):1087-1090.
[13]张福云,王文华,陈琳,等.暖宫七味散对原发性痛经寒凝血滞证患者血清PGF2α、PGE2水平及子宫微循环的影响[J].中国现代医生,2017,55(23):10-12,16.
[14] Liedman R,Hansson SR,Howe D,et al. Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects[J]. Gynecol Endocrinol,2008,24(9):508-513.
[15] Shangold MM,Aksel S,Schomberg DW,et al. Plasma prostaglandin F2-alpha levels in dysmenorrehic women[J].Fertil Steril,1976,27(10):1171-1175.
[16]齐丹丹,张玲,申松希,等.不同针刺刺激量对寒凝证类痛经模型大鼠扭体反应及子宫内前列腺素物质含量的影响[J].中医药信息,2015,32(4):48-51.
[17]贾小红,巩海亮,宋兰英,等.针刺治疗对原发性痛经患者性激素及前列腺素分泌的调节作用[J].中国医药导报,2016,13(7):76-79.
[18]崔静宜.复方金铃四逆四物失笑散对原发性痛经大鼠模型的作用机制[D].成都:成都中医药大学,2016:1-41.
[19]方玲,朱新冰,尹菊,等.经前三剂止痛方治疗实验性痛经模型大鼠作用机制研究[J].天津中医药,2010,27(1):46-49.
[20]庄惠琴.疏肝化瘀汤治疗气滞血瘀型原发性痛经的临床疗效观察[J].中国当代医药,2016,23(12):119-121.
[21]陆煜,马瑞芬,钱黎.温针灸治疗原发性痛经的临床效果与安全性评价[J].中国现代医生,2018,56(8):134-136,140.
[22]秦丽娟,卫红霞,郭述真.β-内啡肽与女性生殖内分泌[J].山西医科大学学报,2007,38(4):361-364.
[23]宋卓敏,屈彩芹,张远,等.痛经宁颗粒对痛经大鼠中枢及外周β-EP含量的影响[J].天津中医药,2004,21(5):405-407.
[24]周杰,陈贞羽,龚杰,等.不同参数组合电针对SNL大鼠镇痛效应观察及对下丘脑内啡肽的影响[J].中国医药导报,2017,14(23):18-21.
[25]刘群,黄欣,苏乐群.元胡白芷配方对大鼠外周血中致痛和镇痛物质的影响[J].中国医院药学杂志,2012,32(8):593-596.
[26]韩彦琪,许浚,张喜民,等.基于网络药理学的元胡止痛滴丸治疗原发性痛经的作用机制研究[J].药学学报,2016,51(3):380-387.
[27]张新庄,柯志鹏,李娜,等.从网络角度研究元胡止痛胶囊治疗头痛与痛经的分子作用机制[J].中国新药杂志,2016,25(20):2323-2330.
[28]段英丹,杨璐,柴程芝,等.麻黄中的主要活性成分对原发性痛经模型小鼠的作用研究[J].世界中西医结合杂志,2018,13(3):344-347,352.
[29]齐丹丹,张梅,郭孟玮,等.不同针刺刺激量对寒凝证类痛经模型大鼠血清及子宫组织内钙离子的影响[J].中医药导报,2015,21(7):1-5.