生化散瘕汤调控Fas/FasL信号通路对人工流产后大鼠子宫内膜损伤的影响  

Effect of Shenghua Sanjia decoction on endometrial damage after induced abortion in rats by regulating Fas/FasL signaling pathway

作　　者：张久严 时娟娟 张丹 ZHANG Jiuyan;SHI Juanjuan;ZHANG Dan(Department of Pharmacy,Tengzhou Central People’s Hospital,Tengzhou277599,China;Department of Gynecology,Tengzhou Central People’sHospital,Tengzhou277599,China)

机构地区：[1]滕州市中心人民医院药学部,山东滕州277599 [2]滕州市中心人民医院妇一科,山东滕州277599

出　　处：《中国医科大学学报》2025年第1期30-37,43,共9页Journal of China Medical University

基　　金：山东省中医药科技项目(2021M102)。

摘　　要：目的探讨生化散瘕汤调控Fas/Fas配体(FasL)信号通路对大鼠人工流产后子宫内膜损伤的影响。方法将妊娠成功的50只大鼠随机分为正常对照组,模型组,低、高剂量(12.6 g/kg、25.2 g/kg)生化散瘕汤组和地屈孕酮(3 mg/kg)组,每组10只。除正常对照组外,其他各组大鼠采用16.6 mg/kg米非司酮联合100μg/kg米索前列醇构建人工流产模型,并采用机械损伤法建立人工流产后子宫内膜损伤模型。给予相应的药物干预后,酶联免疫吸附试验(ELISA)检测血清中雌激素(E_(2))、孕激素(P)、催乳素(PRL)含量;HE染色检测子宫内膜组织病理学改变;Masson染色检测子宫内膜组织纤维化;原位末端转移酶标记法(TUNEL)检测子宫内膜组织中细胞凋亡;实时定量PCR检测子宫内膜组织中雌激素受体(ER)、孕激素受体(PR)、催乳素受体(PRLR)、血管内皮生长因子(VEGF)、Fas、FasL mRNA表达;Western blotting检测子宫内膜组织中转化生长因子-β(TGF-β)、基质金属蛋白酶-9(MMP-9)、Fas、FasL蛋白表达。结果与正常对照组比较,模型组大鼠血清中E_(2)、P、PRL含量,子宫内膜组织中ER、PR、PRLR、VEGF mRNA表达,MMP-9蛋白表达水平均降低;子宫内膜组织中细胞凋亡率,Fas、FasL mRNA表达,TGF-β、Fas、FasL蛋白表达均升高(均P<0.05);子宫内膜组织严重受损,胶原纤维增多。与模型组比较,低、高剂量生化散瘕汤组和地屈孕酮组大鼠血清中E_(2)、P、PRL含量,子宫内膜组织中ER、PR、PRLR、VEGF mRNA表达,MMP-9蛋白表达均升高;子宫内膜组织中细胞凋亡率,Fas、FasL mRNA表达,TGF-β、Fas、FasL蛋白表达均降低(均P<0.05);子宫内膜组织病理学损伤减轻,胶原纤维减少。结论生化散瘕汤能够减轻人工流产后大鼠子宫内膜纤维化和细胞凋亡,促进子宫内膜修复,其机制可能与抑制Fas/FasL信号通路激活有关。Objective To investigate the effect of the Shenghua Sanjia decoction on endometrial damage after induced abortion in rats by regulating the Fas/Fas ligand(FasL)signaling pathway.Methods Fifty pregnant rats were randomly assigned to five groups:normal control,model,low-and high-dose Shenghua Sanjia decoction(12.6 g/kg and 25.2 g/kg,respectively),and dydrogesterone(3 mg/kg)groups,with 10 rats in each group.In all groups except the normal control group,rats were administered 16.6 mg/kg mifepristone combined with 100μg/kg misoprostol to establish an artificial abortion model,and the endometrial injury model was established by a mechanical injury method.After administering the respective drug intervention,enzyme-linked immunosorbent assay(ELISA)was used to measure serum levels of estrogen(E_(2)),progesterone(P),and prolactin(PRL).Histopathological changes of the endometrium were evaluated using HE staining.Masson staining was employed to assess endometrial fibrosis,whereas TdT-mediated dUTP nick-end labeling(TUNEL)was utilized to detect apoptosis in the endometrial tissue.Additionally,the mRNA expression levels of the estrogen receptor(ER),progesterone receptor(PR),prolactin receptor(PRLR),vascular endothelial growth factor(VEGF),Fas,and FasL in the endometrial tissue were measu-red using real-time quantitative PCR.Finally,Western blotting was performed to analyze the protein expression levels of transforming growth factor-β(TGF-β),matrix metalloproteinase-9(MMP-9),Fas,and FasL in the endometrial tissue.Results Compared to the normal control group,the model group showed a decreased E_(2),P,and PRL serum levels,a reduction in the mRNA expressions of ER,PR,PRLR,and VEGF as well as decreased protein expression of MMP-9 in the endometrial tissue.However,the apoptosis rate,mRNA expression of Fas and FasL,and protein expression of TGF-β,Fas,and FasL in the endometrial tissue were all increased(P<0.05).Lastly,the endometrial tissue was found to be severely damaged with the collagen fibers increased.Compared to the model

关 键 词：生化散瘕汤 人工流产 Fas/Fas配体信号通路 子宫内膜损伤 大鼠 

分 类 号：R714.2[医药卫生—妇产科学]