盐酸贝那普利对TGF-β1诱导的子宫内膜上皮及间质细胞纤维化的保护作用研究  

Protective effect of benazepril hydrochloride on fibrosis of endometrial epithelial and mesenchymal cells induced by TGF-β1

作　　者：罗星雨 转黎 胥琴 田冀雯 马艳萍[2] LUO Xing-yu;ZHUAN Li;XU Qin;TIAN Ji-wen;MA Yan-ping(Affiliated Hospital of Kunming University of Science and Technology,Kunming 650093,China;Department of Reproductive Medicine,the First People′s Hospital of Yunnan Province,Kunming 650032,China)

机构地区：[1]昆明理工大学附属医院,云南昆明650093 [2]云南省第一人民医院生殖医学科,云南昆明650032

出　　处：《实用药物与临床》2022年第7期577-583,共7页Practical Pharmacy and Clinical Remedies

基　　金：国家自然科学基金(81660247 KCNN3/SK3);国家自然科学基金(81760470 Sema4C);云南省卫生和计划生育委员会医学学科带头人培养计划(D-2019018);云南省卫生和计划生育委员会医学后备人才培养计划(H2017025)。

摘　　要：目的探索盐酸贝那普利对转化生长因子β1(TGF-β1)诱导人子宫内膜上皮及间质细胞纤维化的保护作用及其可能机制。方法将人子宫内膜上皮细胞(AN3CA)及人子宫内膜间质细胞(hESC)用TGF-β1诱导纤维化。分为对照组、实验组(TGF-β15 ng/ml处理)、BNPL5组(TGF-β15 ng/ml+盐酸贝那普利5μmol/L处理)和BNPL8组(TGF-β15 ng/ml+盐酸贝那普利8μmol/L处理),AN3CA细胞共培养48 h,hESC细胞共培养72 h,镜下观察细胞形态,CellTiter-Glo检测细胞活力,流式细胞仪检测细胞凋亡情况,蛋白质印迹法检测相应纤维化蛋白。结果盐酸贝那普利可部分逆转TGF-β1对AN3CA细胞的形态学改变,hESC细胞经过TGF-β1处理后形态无明显变化;促进TGF-β1诱导后的AN3CA细胞的增殖活力,降低AN3CA细胞凋亡水平(实验组:12.11±0.465,BNPL8组:7.68±0.818,P<0.001);抑制TGF-β1诱导后的hESC细胞的增殖活力,促进其细胞凋亡(实验组:7.553±0.688,BNPL8组:11.047±0.118,P=0.016);盐酸贝那普利诱导后AN3CA及hESC细胞相关纤维化因子Fibronectin、TGF-β1、smad3的表达均有下降。结论盐酸贝那普利可以改善TGF-β1诱导的子宫内膜上皮及间质细胞的纤维化改变。Objective To explore the protective effect of benazepril hydrochloride on TGF-β1-induced fibrosis of human endometrial epithelial and mesenchymal cells and its possible mechanism.Methods Human endometrial epithelial cells(AN3CA)and human endometrial stromal cells(hESC)were treated with TGF-β1 to induce fibrosis.The experiment included control group,experimental group(TGF-β15 ng/ml),BNPL5 group(TGF-β15 ng/ml+Benazepril hydrochloride 5μmol/L)and BNPL8 group(TGF-β15 ng/ml+Benazepril hydrochloride 8μmol/L);AN3CA cells were co-cultured for 48 hours and hESC cells were co-cultured for 72 hours.Cell morphology was observed under microscope,cell viability was detected by Celltiter-Glo,and cell apoptosis was detected by flow cytometry.The corresponding fibrotic proteins were detected by Western blot.Results Benazepril hydrochloride partially reversed the morphological changes of AN3CA cells induced by TGF-β1,while hESC cells showed no significant morphological changes after TGF-β1 treatment.Benazepril hydrochloride could promote the proliferation of AN3CA cells induced by TGF-β1,and reduce the apoptosis level of AN3CA cells(experimental group:12.11±0.465;BNPL8 group:7.68±0.818,P<0.001).It could inhibit the proliferation of hESC cells induced by TGF-β1 and promote their apoptosis(experimental group:7.553±0.688,BNPL8 group:11.047±0.118,P=0.016).The expression of AN3CA and hESC cell-related fibrosis factors,including Fibronectin,TGF-β1 and Smad3,decreased after benazepil hydrochloride induction.Conclusion Benazepril hydrochloride can improve the fibrotic changes of endometrial epithelial and mesenchymal cells induced by TGF-β1.

关 键 词：TGF-Β1 人子宫内膜上皮细胞 人子宫内膜间质细胞 宫腔粘连 盐酸贝那普利 

分 类 号：R711[医药卫生—妇产科学]