摘要
目的研究重组人内皮抑素对子宫内膜异位症(EMs)大鼠的治疗作用,以及对基质金属蛋白酶(MMP)蛋白表达的影响。方法用自体子宫内膜移植法建立大鼠EMs模型,假手术组(n=10)仅结扎右侧子宫角。将建模成功大鼠随机分为模型组(n=12)、实验组(n=12)和对照组(n=12)。实验组和对照组分别灌胃给予2.5 mg·kg^-1重组人内皮抑素和达那唑0.02 g·kg^-1,模型组和假手术组则灌胃给予等量生理盐水,每日1次,均连续干预2周。用酶联免疫吸附(ELISA)法测定大鼠血清炎性因子及血管内皮生长因子(VEGF)指标水平,以免疫组化检测大鼠异位内膜组织中CD34表达,计算微血管密度(MDV),以蛋白质印迹法(WB)检测各组异位组织中金属基质蛋白酶-2(MMP-2)、金属基质蛋白酶-9(MMP-9)、组织型基质金属蛋白酶抑制因子-1(TIMP-1)蛋白表达。结果干预后,假手术组、模型组、实验组和对照组大鼠异位病灶组织中MDV分别为5.69±2.36,23.16±3.45,10.24±2.46,9.68±2.74,血清中白细胞介素-6(IL-6)分别为(35.12±4.26),(79.58±6.12),(48.69±5.20)(43.26±3.59)ng·L^-1,VEGF分别为(36.45±2.69),(68.52±1.45),(52.34±1.69),(46.28±5.13)ng·L^-1,MMP-2蛋白相对表达量分别为0.23±0.05,1.35±0.24,0.34±0.06,0.45±0.16,MMP-9蛋白相对表达量分别为0.26±0.03,1.52±0.32,0.48±0.07,0.52±0.05,TIMP-1蛋白相对表达量分别为1.24±0.12,0.32±0.05,0.89±0.12,0.86±0.14,实验组和对照组分别与模型组比较,差异均有统计学意义(均P<0.05)。结论重组人内皮抑素可有效促进EMs大鼠异位子宫内膜萎缩,减轻机体炎性反应,与其显著下调MMP蛋白表达,调控MMP-9/TIMP-1平衡有关。
Objective To investigate the therapeutic effect of recombinant human endostatin on endometriosis(EMs)rats and the expression of matrix metalloproteinase(MMP).Methods Rat models were established by autologous endometrial transplantation.In sham operation group(n=10),only the right uterine horn was ligated.Successful rats were randomly divided into model group(n=12),test group(n=12)and control group(n=12).Test group and control group were given 2.5 mg·kg^-1 recombinant human endostatin and 0.02 g·kg^-1 danazol respectively,while model group and sham operation group were given the same amount of normal saline,once a day for 2 weeks.The levels of serum inflammatory factors and vascular endothelial growth factor(VEGF)were measured by ELISA.The expression of CD34 in ectopic intima ofrats was detected by immunohistochemistry,and the microvessel density(MDV)was calculated.Matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9)and tissue matrix metalloproteinase inhibitor-1(TIMP-1)were detected by Western blot(WB).Results After intervention,the MDV of ectopic lesions in sham-operation group,model group,test group and control group were 5.69±2.36,23.16±3.45,10.24±2.46 and9.68±2.74,serum IL-6 were(35.12±4.26),(79.58±6.12),(48.69±5.20),(43.26±3.59)ng·L^-1,VEGF were(36.45±2.69),(68.52±1.45),(52.34±1.69),(46.28±5.13)ng·L^-1,the relative expression of MMP-2 protein were 0.23±0.05,1.35±0.24,0.34±0.06,0.45±0.16,the relative expression of MMP-9 protein were 0.26±0.03,1.52±0.32,0.48±0.07,0.52±0.05,and the relative expression of TIMP-1 protein were 1.24±0.12,0.32±0.05,0.89±0.12,0.86±0.14,the differences in test group and control group comparied with model group were significant(all P<0.05).Conclusion Recombinant human endostatin can effectively promote the atrophy of ectopic uterus and reduce the inflammatory reaction in EMs rats,which is related to the down-regulation of MMP protein expression and the regulation of MMP-9/TIMP-1 balance.
作者
肖艳平
付久园
王晓华
葛永梅
朱艳菊
XIAO Yan-ping;FU Jiu-yuan;WANG Xiao-hua;GE Yong-mei;ZHU Yan-ju(Department of Obstetrics,Affiliated Hospital of Chengde Medical College,Chengde 067000,Hebei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2019年第22期2881-2883,共3页
The Chinese Journal of Clinical Pharmacology
基金
承德市科学技术研究与发展计划基金资助项目(201606A057)
