白果内酯对子宫肌瘤细胞及裸鼠移植瘤的影响实验研究  

Effects of bilobalide on uterine leiomyoma cells and transplantable tumors in nude mice

作　　者：汤友苗 孔成才 范文秀 周青 曹景云 TANG Youmiao;KONG Chengcai;FAN Wenxiu;ZHOU Qing;CAO Jingyun(Changzhou Maternal and Child Health Care Hospital,Changzhou Medical Center,Nanjing Medical University,Changzhou 213300,China;Affiliated Jinling Hospital,Medical School of Nanjing University,Nanjing 210002,China)

机构地区：[1]南京医科大学常州医学中心常州市妇幼保健院,江苏常州213300 [2]南京大学医学院附属金陵医院,江苏南京210002

出　　处：《陕西医学杂志》2025年第2期152-157,共6页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(81901890);江苏省常州市科技项目(CJ20210135)。

摘　　要：目的:探究白果内酯对子宫肌瘤细胞及裸鼠移植瘤的影响。方法:收集18例子宫肌瘤患者术后组织标本,分离和培养子宫肌瘤细胞,并将其分为对照组(无处理)、低剂量白果内酯组(10μmol/L白果内酯处理)、中剂量白果内酯组(50μmol/L白果内酯处理)和高剂量白果内酯组(100μmol/L白果内酯处理)。采用CCK-8法检测细胞活性,流式细胞仪检测细胞凋亡及细胞周期分布情况,Western blot检测细胞外基质相关蛋白表达。将人原代子宫平滑肌瘤细胞于腹部皮下注射入雌性裸鼠体内建立裸鼠移植瘤模型。当移植瘤大小达到50~100 mm^(3)时,将裸鼠随机分为对照组和白果内酯组,每组60只。白果内酯组给予腹腔注射白果内酯10 mg/kg,每周2次,连续4周;对照组按照同样频率给予腹腔注射0.9%氯化钠溶液10 mg/kg。于干预后第0、7、14、21、28、35、42、49、56、66天分离肿瘤并测量其大小,计算移植瘤体积。采用免疫组织化学法检测组织增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)表达。采用Western blot检测组织生长相关蛋白表达。结果:与对照组比较,低、中、高剂量白果内酯组子宫肌瘤细胞活性逐渐降低,细胞凋亡率逐渐升高(均P<0.05)。与对照组比较,中、高剂量白果内酯组阻滞在G1期的子宫肌瘤细胞比例逐渐增加(均P<0.05)。与对照组和低剂量白果内酯组比较,中、高剂量白果内酯组子宫肌瘤细胞纤维连接蛋白(Fibronectin)、Ⅰ型胶原(COL1A1)、波形蛋白(Vimentin)、α-SMA和β-连环蛋白(β-catenin)蛋白水平逐渐降低(均P<0.05)。与对照组比较,从干预后第49天起白果内酯组移植瘤体积显著缩小(均P<0.05)。与对照组比较,白果内酯组PCNA和α-SMA蛋白阳性细胞比例以及PCNA和Fibronectin蛋白表达水平降低,Bax/Bcl-2比值升高(均P<0.05)。结论:白果内酯能够促进子宫肌瘤细胞凋亡,诱导其发生G1期阻滞,抑制裸鼠子宫肌瘤移植瘤生�Objective:To investigate the effects of bilobalide on uterine leiomyoma cells and transplantable tumors in nude mice.Methods:Postoperative tissue specimens were collected from 18 patients with uterine leiomyomas,and uterine leiomyoma cells were isolated and cultured.The cells were divided into a control group(no treatment),a low-dose bilobalide group(treated with 10μmol/L bilobalide),a medium-dose bilobalide group(treated with 50μmol/L bilobalide)and a high-dose bilobalide group(treated with 100μmol/L bilobalide).Cell viability was assessed using the CCK-8 method,apoptosis and cell cycle distribution were detected by flow cytometry,and the expression of extracellular matrix-related proteins was examined by Western blot.A nude mouse transplantable tumor model was established by subcutaneously injecting primary human uterine leiomyoma cells into the abdomens of female nude mice.When the transplantable tumors reached a size of 50~100 mm^(3),the nude mice were randomly divided into a control group and a bilobalide group,with 60 mice in each group.The bilobalide group was treated with intraperitoneal injections of bilobalide at a dose of 10 mg/kg twice a week for 4 weeks;the control group was treated with intraperitoneal injections of 0.9%sodium chloride solution at the same frequency and dose.At 0,7,14,21,28,35,42,49,56 and 66 days after intervention,tumors were isolated and measured,and the volume of transplanted tumors was calculated.The expression of PCNA andα-SMA was detected by immunohistochemistry,and the expression of growth-related proteins was assessed by Western blot.Results:Compared with the control group,the cell viability of the low,medium and high-dose bilobalide groups gradually decreased,and the apoptosis rate gradually increased(all P<0.05).Compared with the control group,the proportion of uterine leiomyoma cells in the G 1 phase was gradually increased in the medium and high-dose bilobalide groups(all P<0.05).Compared with the control group and the low-dose bilobalide group,the protein levels of

关 键 词：子宫肌瘤 白果内酯 细胞凋亡 细胞周期 移植瘤 裸鼠 

分 类 号：R36[医药卫生—病理学]