加味复方三棱丸对大鼠子宫内膜异位症血管生成及其侵袭性的影响  

Effect of tranditional Chinese medical compounds san-leng-wan on angiogenesis and invasion of endometriosis in rats

作　　者：叶兰 陈怡[2] 何正光[3] 陈刚[4] 徐晓玉[2] YE Lan;CHEN Yi;HE Zhengguang;CHEN Gang;XU Xiaoyu(Department of Basic Medical Sciences,Guizhou Medical University,Guiyang 550025,Guizhou,China;College of Pharmaceutical Sciences,Southwest University,Chongqing 400715,China;Department of Pharmacy,Hospital of Chongqing Normal University,Chongqing 400047,China;Research Center of Medicine,Chongqing Technology and Business University,Chongqing 400067,China)

机构地区：[1]贵州医科大学基础医学院,贵州贵阳550025 [2]西南大学药学院,重庆400715 [3]重庆师范大学医院药剂科,重庆400047 [4]重庆工商大学药物研究中心,重庆400067

出　　处：《贵州医科大学学报》2021年第3期281-287,共7页Journal of Guizhou Medical University

基　　金：国家科技重大专项课题(2010ZX09401-306-3-16);贵州省科技厅基金项目[黔科合J字(2008)2281号]。

摘　　要：目的观察加味复方三棱丸(SLW)对子宫内膜异位症(EMS)大鼠异位组织血管生成及其侵袭性的影响及机制。方法选择动情期大鼠行子宫内膜自体缝合术建立大鼠EMS疾病模型,将40只模型鼠随机均分为模型组、SLW(高、中、低)剂量组和孕三烯酮组,SLW各剂量组和孕三烯酮组每天灌胃对应药物1次,另设正常组8只,正常组及模型组每天以等容积的生理盐水灌胃,均连续灌胃28 d;测量模型组、SLW(高、中、低)剂量组和孕三烯酮组大鼠异位组织的体积,检测各组大鼠血清雌二醇(E2)、孕酮(P)水平、腹腔液中血管内皮生长因子(VEGF)含量,检测正常组大鼠子宫内膜组织和其他组EMS大鼠异位组织中基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制因子-1(TIMP-1)的蛋白和mRNA表达,检测Ⅷ因子并判定微血管密度(MVD)。结果SLW高、中剂量组异位内膜组织体积较模型组减小(P<0.05);与模型组比较,SLW高、中剂量组腹腔VEGF含量降低(P<0.01或P<0.05),SLW高、中、低剂量组大鼠血清E2降低(P<0.05);与模型组比较,SLW高、中、低剂量组异位组织中MMP-9阳性细胞数量减少、染色浅,表达评分分值降低,MMP-9 mRNA的表达也减少(P<0.05);与模型组比较,SLW各剂量组异位组织中TIMP-1阳性细胞数量多且深染,表达评分分值增高,TIMP-1 mRNA的表达也增加(P<0.05);与模型组比较,SLW高、中剂量组大鼠异位组织MVD减少(P<0.05)。结论SLW可以有效控制EMS的发展,其机制可能与抑制异位组织血管新生及降低侵袭能力有关。Objective To observe the therapeutic effect and its mechanism of the tranditional Chinese compounds of san-leng-wan(SLW,composed of sparganii acid,oleum curcumae wenchowensis and notogiseng glycosides)on ectopic endometrium(EMS)in rats.Methods Forty EMS models of rats were established and were divided into the model group,the high,medium,and low dose SLW groups and the gestrinone positive control group.According to the size of grafts.The SLW groups and control group were intragastrically administrated with drugs for 28 days continuously.The volume of ectopic EMS,the level of serum E2 and P were measured.The content of VEGF in peritoneal fluid was detected by ELISA.The expression of MMP-9,TIMP-1,and MVD were tested by routine HE staining and immunohistochemistry.The mRNA expression of MMP-9,TIMP-1 were detected by RT-PCR.Results Four weeks later,the growth of the grafts was observed again.The volume of the grafts in the high and medium dose SLW groups decreased significantly compared with that of the model group(P<0.05).Compared with the model group,the E2 value of the high,medium and low dose SLW groups decreased significantly(P<0.05);immunohistochemistry results showed that the SLW groups had less number of positive cells and lighter staining,with significant difference(P<0.05),and the number of TIMP-1 positive cells in the SLW groups was more than that in the model group(P<0.05).After SLW treatment,the expression of MMP-9 mRNA of EMS was significantly reduced,and there was a significant difference among the SLW groups and the model group(P<0.05).The expression of TIMP-1 mRNA in the SLW groups increased.The relative optical density of the strip in the treatment group was significantly different from that in the model group(P<0.05).Conclusion SLW can effectively control the development of EMS,and its mechanism is related to the inhibition of angiogenesis and the reduction of invasive ability.

关 键 词：子宫内膜异位症 基质金属蛋白酶9 雌二醇 基质金属蛋白酶抑制-1 微血管密度 加味复方三棱丸 

分 类 号：R285.5[医药卫生—中药学]