崇明苦草水提物治疗早孕流产大鼠产后恶露不绝作用及机制研究  

Effect of Chongming Vallisneria natans Water Extract on Postpartum Lochiorrhea in Rats with Abortion During Early Pregnancy and Its Mechanism

作　　者：袁金凤 徐锘 余明珠 沈玮 雷春光 顾佳楠 韩笑 吴辉[1] 侴桂新[1] 石海莲[1] 朱美文[2] 吴晓俊[1] YUAN Jinfeng;XU Nuo;YU Mingzhu;SHEN Wei;LEI Chunguang;GU Jianan;HAN Xiao;WU Hui;CHOU Guixin;SHI Hailin;ZHU Meiwen;WU Xiaojun(Shanghai Key Laboratory of Compound Chinese Medicines,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 200120;Xinhua Hospital Chongming Branch Affliated to Shanghai Jiaotong University School of Medicine,Shanghai 202150)

机构地区：[1]上海中医药大学中药研究所暨上海市复方中药重点实验室,上海200120 [2]上海交通大学医学院附属新华医院崇明分院,上海202150

出　　处：《中药药理与临床》2023年第4期52-57,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：上海市复方中药重点实验室项目(编号:17DZ2273300)。

摘　　要：目的:研究崇明苦草水提物对早孕流产大鼠产后恶露不绝治疗作用及机制。方法:采用米非司酮12.4 mg/kg和米索前列醇0.13 mg/kg建立早孕流产大鼠模型,并将造模大鼠随机分为模型对照组、崇明苦草水提物1、2、4 g/kg组和阳性对照益母草膏3 mL/kg组,受孕大鼠正常生产作为正常对照组。连续给药7 d后,运用紫外分光光度法测定给药期间子宫出血量;血液流变仪检测血流变学变化;测定活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)和纤维蛋白原(FIB)等凝血四项指标;HE染色法观察子宫组织病理学变化;免疫组化染色CD34检测子宫微血管密度(MVD);ELISA法测定血浆血栓素(TXB2)和6-酮前列腺素(6-keto-PGF1α)含量,Westren Blot法和RT-PCR法检测子宫组织血管内皮生长因子(VEGF)蛋白和mRNA表达。结果:与正常对照组相比,模型对照组大鼠子宫出血量显著增多,子宫内膜损伤显著,全血黏度和血浆黏度显著上升,APTT、PT、TT显著延长(P<0.01),而FIB含量显著降低(P<0.01),大鼠子宫宫腔黏膜上皮不完整、黏膜有皱襞或宫腔中有脱落物,内膜明显增厚,子宫中MVD显著减少(P<0.01),血浆TXB2含量显著降低(P<0.01),而6-keto-PGF1α含量显著升高(P<0.01);TXB2/6-keto-PGF1α的浓度分数显著降低(P<0.01),子宫组织Vegf mRNA和蛋白表达显著上调(P<0.01);与模型对照组相比,崇明苦草水提物2、4 g/kg组子宫出血量明显减少,全血黏度降低,凝血时间缩短(P<0.05或P<0.01),而FIB含量明显升高(P<0.05或P<0.01),残留的蜕膜组织和绒毛减少,子宫内膜修复较好,MVD明显增加(P<0.05或P<0.01),血浆中TXB2含量明显升高,6-keto-PGF1α的含量明显降低(P<0.05),TXB2/6-keto-PGF1α的浓度分数明显增加(P<0.05或P<0.01);崇明苦草水提物各组均明显下调子宫组织VEGF蛋白表达(P<0.05或P<0.01);4 g/kg组子宫组织中Vegf mRNA过度表达显著下调(P<0.01)。结论:崇明苦草水提物显著改善产�Objective:To study the therapeutic effect of Chongming Vallisneria natans water extract(CWE)on postpartum lochiorrhea in rats with abortion during early pregnancy and its mechanism.Methods:The rat model of abortion during early pregnancy was induced by mifepristone(12.4 mg/kg)and misoprostol(0.13 mg/kg).The modeling rats were randomly divided into a model group,three CWE low,medium,and high-dose groups(1 g/kg,2 g/kg,and 4 g/kg),and a positive control Yimucao ointment group(3 mL/kg).The pregnant rats giving birth normally were set as the normal control group.After administration for 7 days,the uterine bleeding volume during administration was detected by ultraviolet spectrophotometry.Changes in blood rheology were detected by a blood rheometer.Four blood coagulation indexes,including activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),and fibrinogen(FIB)were detected by an automatic blood coagulation analyzer.Pathological changes in the endometrium were observed by hematoxylin-eosin(HE)staining.Microvascular density(MVD)in uterine tissues was detected by immunohistochemical staining with CD34.The content of thromboxane B-2(TXB-2)and 6-Keto-prostaglandin-1α(6-Keto-PGF-1α)in the plasma of rats was determined by enzyme-linked immunosorbent assay(ELISA).The protein and mRNA expression levels of vascular endothelial growth factor(VEGF)in the uterine tissues were determined by Western blot and real-time quantitative polymerase chain reaction(RT-PCR).Results:As compared with the normal control group,the uterine bleeding volume and endometrial injury increased significantly in the model group.The whole blood viscosity and plasma viscosity increased,and the APTT,PT,and TT were prolonged in the model group(P<0.01),while the FIB content was decreased(P<0.01).In the model group,the epitheli-um mucosa in the uterus was incomplete,duplicature and uterine exfoliation were observed,the endometrium was obviously thickened,and the MVD level was decreased(P<0.01).The serum content of TXB-2 was reduce

关 键 词：崇明苦草水提物 产后恶露不绝 止血作用 血液流变学 子宫内膜修复 子宫微血管 

分 类 号：R285.5[医药卫生—中药学]