散结镇痛胶囊对缩宫素诱导小鼠痛经的作用机制  

Action mechanism of Sanjie Zhentong Capsules in oxytocin⁃induced dysmenorrhea in mouse models

作　　者：孙兰 李家春 刘莉娜[3,4] 皇立卫 魏天杨 王振中[3,4] SUN Lan;LI Jia-chun;LIU Li-na;HUANG Li-wei;WEI Tian-yang;WANG Zhen-zhong(Jiangsu Food and Pharmaceutical Science College,Huai’an 223003,China;Jiangsu Vocational College of Finance and Economics,Huai’an 223003,China;Jiangsu Kanion Pharmaceutical Co.,Ltd.,Lianyungang 222001,China;State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process,Lianyungang 222001,China)

机构地区：[1]江苏食品药品职业技术学院,江苏淮安223003 [2]江苏财经职业技术学院,江苏淮安223003 [3]江苏康缘药业股份有限公司,江苏连云港222001 [4]中药制药过程新技术国家重点实验室,江苏连云港222001

出　　处：《中成药》2021年第8期2030-2035,共6页Chinese Traditional Patent Medicine

基　　金：国家科技部国家重大新药创制专项(2013ZX09402203);江苏食品药品职业技术学院院级项目(YY20200017,Jsfpcyjy2019006)。

摘　　要：目的研究散结镇痛胶囊对缩宫素诱导小鼠痛经模型的镇痛机制。方法将60只ICR雌性小鼠按体质量随机分为正常组、模型组、阳性组(布洛芬缓释胶囊,0.10 g/kg),散结镇痛胶囊高、中、低剂量组(1.80、0.90、0.45 g/kg)组。采用注射苯甲酸雌二醇和缩宫素复制小鼠痛经模型,注射激素的同时开始每天灌胃给药,连续7 d。末次灌胃1 h后,除正常组外,其余组各鼠腹部注射缩宫素2 IU,并记录30 min内小鼠扭体反应次数。小鼠取血后颈椎脱臼处死,分离子宫组织,检测血清中E2、NO水平及子宫组织PGF_(2α)(前列腺素F2α)、Ca^(2+)水平和P⁃MLC20(磷酸化肌球蛋白轻链)、COX⁃2(环氧合酶⁃2)、ERα(雌激素受体)蛋白表达。结果与模型组比较,散结镇痛胶囊抑制缩宫素诱导的小鼠扭体反应(P<0.05,P<0.01),散结镇痛胶囊能够降低血清中E2水平及升高NO水平(P<0.05,P<0.01)。与正常组比较,模型组小鼠子宫组织PGF_(2α)、Ca^(2+)水平升高(P<0.01),P⁃MLC20、COX⁃2蛋白表达增加(P<0.01);与模型组比较,散结镇痛胶囊高、中剂量组可降低缩宫素诱导痛经小鼠子宫组织PGF_(2α)、Ca^(2+)水平(P<0.05,P<0.01)及P⁃MLC20、COX⁃2蛋白表达(P<0.05,P<0.01);散结镇痛胶囊低剂量组也能降低子宫组织PGF_(2α)、Ca^(2+)水平(P<0.05,P<0.01)及COX⁃2蛋白表达(P<0.05)。结论散结镇痛胶囊抑制缩宫素诱导的小鼠痛经作用机制与减少P⁃MLC20、COX⁃2、ERα蛋白表达,降低PGF_(2α)、Ca^(2+)、E2水平相关。AIM To clarify the mechanism of analgesic effect of Sanjie Zhentong Capsules on oxytocin⁃induced dysmenorrhea in mouse models.METHODS Sixty ICR female mice were randomly divided into normal group,model group,ibuprofen group(0.1 g/kg)and Sanjie Zhentong Capsules groups for high⁃dose,mid⁃dose,and low⁃dose uses(1.80,0.90,0.45 g/kg).The induction of dysmenorrhea mouse models with injection of estradiol benzoate and oxytocin,and 7 d intragastric administration of the corresponding drug were initiated simultaneously.1h after the completion of last intragastric feeding,2 IU peritoneal injection of oxytocin was given to the mice except those of the normal group,after which the number of writhing was recorded within 30 min.After blood collection at eyepit,the mice were euthanized by cervical dislocation and had uteruses removal for the determinations of serum contents of E2 and NO,uteric levels of PGF_(2α) and Ca^(2+),and protein expressions of phosphorylated myosin light chain(P⁃MLC20),cyclooxygenase⁃2(COX⁃2),and ERαas well.RESULTS Compared with the model group,Sanjie Zhentong Capsules groups shared inhibited oxytocin⁃induced writhing(P<0.05,P<0.01);decreased E2 level and increased NO level in serum(P<0.05,P<0.01).Compared with the normal group,the model group displayed increased uteric levels of PGF_(2α)and Ca^(2+) (P<0.01),and increased protein expressions of P⁃MLC20 and COX⁃2(P<0.01).Compared with the model group,groups dosed with high⁃dose and moderate⁃dose Sanjie Zhentong Capsules shared decreased uteric levels of PGF_(2α)and Ca^(2+) (P<0.05,P<0.01),and reduced protein expressions of P⁃MLC20 and COX⁃2(P<0.05,P<0.01).Low⁃dose Sanjie Zhentong Capsules reduced the uteric levels of PGF_(2α) and Ca^(2+) (P<0.05,P<0.01),and the expression of COX⁃2 protein(P<0.05).CONCLUSION The inhibitory mechanism of Sanjie Zhentong Capsules in oxytocin⁃induced dysmenorrhea in mice is associated with the reduction of P⁃MLC20,COX⁃2 and ERαprotein expression and the decrease of PGF_(2α),Ca^(2+)

关 键 词：散结镇痛胶囊 缩宫素 痛经 前列腺素F_(2α) 

分 类 号：R285.5􀆰[医药卫生—中药学]