基于COX2-PGE2途径探讨盆痛灵对气滞血瘀型EM大鼠的镇痛作用  

Study on the Analgesic Effect of Pentongling Formula on Rats with EM of Qi Stagnation and Blood Stasis Syndrome Based on COX2-PGE2 Pathway

作　　者：李宣儒 夏玉 王丽[2] 余思云 刘晓庆 付金荣[3] LI Xuanru;XIA Yu;WANG Li;YU Siyun;LIU Xiaoqing;FU Jinrong(Longhua Clinical Medical College,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Shanghai Ninth People s Hospital,Shanghai JiaoTong Univesity School of Medicine,Shanghai 200011,China;Department of Gynecology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学龙华临床医学院,上海200032 [2]上海交通大学医学院附属第九人民医院,上海200011 [3]上海中医药大学附属龙华医院妇科,上海200032

出　　处：《中国民族民间医药》2023年第18期12-18,共7页Chinese Journal of Ethnomedicine and Ethnopharmacy

基　　金：国家自然科学基金资助项目(81674009)。

摘　　要：目的:采用夹尾联合自体移植的方法,建立气滞血瘀型内异症(EM)大鼠模型,探讨盆痛灵方对其的镇痛作用及其机制。方法:EM造模后随机分组,A组(EM造模1周后夹尾),B组(EM造模不夹尾),C组(EM造模1周后夹尾加中药盆痛灵干预),另设假手术组:D组(假手术1周后夹尾),E组(假手术不夹尾)。通过观察大鼠的日常行为特征,测量大鼠不同时间点痛阈,检测大鼠血液流变学指标,对气滞血瘀型EM疼痛模型的模型质量进行评价。测量大鼠给药前后内异灶体积。ELISA检测大鼠雌二醇(E2)与前列腺素E2(PGE2)水平,免疫组化、RT-qPCR检测大鼠环氧合酶-2(COX-2)蛋白和COX-2mRNA的表达。结果:A组(EM+夹尾)、D组(假手术+夹尾)夹尾造模后舌色瘀紫,暴躁易怒。A组(EM+夹尾)与B组(EM不夹尾)比较,D组(假手术+夹尾)与E组(假手术不夹尾)比较:其他条件相同时,进行夹尾造模的组痛阈更低(P<0.05),血液流变学水平上升(P<0.05),COX-2蛋白,COX-2mRNA和E2,PGE2表达增高(A:P<0.05,P<0.001,P<0.001,P<0.01/D:P<0.01,P<0.01,P<0.001,P<0.001)。C组(EM+夹尾+中药)治疗后舌色淡粉,性格温和。与A组(EM+夹尾+生理盐水)比较,其内异灶缩小(P<0.001);给药4周后痛阈升高(P<0.001);血液流变学水平下降(P<0.05);COX-2蛋白,COX-2mRNA和E2,PGE2表达降低(P<0.001,P<0.01,P<0.001,P<0.001)。结论:采用夹尾联合自体移植可成功制造气滞血瘀型EM大鼠疼痛模型,通过大鼠行为学特征,血液流变学,痛阈三方面对模型质量进行评价。盆痛灵方能改变大鼠行为学特征,缩小内异灶体积,改善血液流变学水平,提高痛阈值,其作用机理为通过抑制大鼠体内COX-2,PGE2和E2的表达水平,从而起到镇痛作用。Objective The rat model of endometriosis(EM)with qi stagnation and blood stasis was established by tail clamping combined with autotransplantation,and the analgesic effect and mechanism of Pentongling Recipe were discussed.Methods After EM modeling,they were randomly divided into A group(EM modeling with tail clamping after one week),B group(EM modeling without tail clamping)and C group(tail clipping after one week of EM modeling,and treat with traditional Chinese medicine).Set up sham operation group:D group(sham operation with tail clipping)and E group(sham operation without tail clipping).By observing the daily behavior characteristics of rats,measuring the pain threshold of rats at different time points,and detecting the hemorheology indexes of rats,the model quality of endometriosis pain model with qi stagnation and blood stasis was evaluated.The volume of endometriosis foci in rats was measured before and after administration.The levels of estradiol(E2)and prostaglandin E2(PGE2)in rats were detected by ELISA,and the expressions of cyclooxygenase-2(COX-2)protein and COX-2mRNA in rats were detected by immunohistochemistry and RT-qPCR.Results Group A(EM+tail clipping)and group D(sham operation+tail clipping)had purple tongue color and irritability after tail clipping.Compared with group A(EM+tail clipping)and group B(EM without tail clipping),group D(sham operation+tail clipping)and group E(sham operation without tail clipping),the pain threshold of the model group with tail clipping was lower when other conditions were the same(P<0.05),the level of hemorheology increased(P<0.05),the expression of COX-2 protein,COX-2mRNA,E2 and PGE2 increased(A:P<0.05,P<0.001,P<0.001,P<0.01/D:P<0.01,P<0.01,P<0.001,P<0.001).Group C(EM+tail clipping+traditional Chinese medicine)had light pink tongue and mild personality after treatment.Compared with group A(EM+tail clipping+normal saline),its ectopic focus volume were smaller(P<0.001);Pain threshold increased after 4 weeks(P<0.001).The level of hemorheology decreased(P<0.05);The

关 键 词：盆痛灵方 气滞血瘀 E2 COX-2 PGE2 

分 类 号：R285.5[医药卫生—中药学]