红藤方从Hippo/YAP通路抑制子宫腺肌症纤维化的机制研究  

Study on the mechanism of Hongteng Decoction in inhibiting adenomyosis fibrosis from Hippo/YAP pathway

作　　者：曾薇薇[1] 陈欣敏[1] 陆黎娟[2] 黄圣惠 曹阳[3] 张婷婷[3] Weiwei Zeng;Xinmin Chen;Lijuan Lu;Shenghui Huang;Yang Cao;Tingting Zhang(Department of Obstetrics and Gynecology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Gynecology,Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine,Suzhou 215007,China;Department of Gynecology,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200083,China)

机构地区：[1]上海中医药大学附属曙光医院妇产科,上海201203 [2]南京中医药大学附属苏州市中医医院妇科,苏州215007 [3]上海中医药大学附属岳阳中西医结合医院妇科,上海200083

出　　处：《国际中医中药杂志》2024年第7期867-873,共7页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82004398)。

摘　　要：目的通过观察红藤方对子宫腺肌症(ADS)小鼠子宫组织上皮细胞间充质转化(EMT)、成纤维细胞向肌成纤维细胞转化(FMT)及Hippo通路中关键蛋白的影响, 探讨红藤方抑制ADS纤维化的作用机制。方法将小鼠按随机数字表法分为空白组、模型组、红藤方组、维替泊芬组, 每组8只。小鼠出生当日为第0天, 从第1天开始, 模型组、红藤方组、维替泊芬组小鼠灌胃1 mg/kg他莫昔芬溶剂, 连续给药 5 d。造模后第42天, 经HE染色验证造模成功。第43天开始, 红藤方组小鼠每日灌胃红藤方水煎液16.5 g/kg, 每3日腹腔注射0.9%NaCl溶液(100 μl/10 g);维替泊芬组小鼠每3日腹腔注射维替泊芬溶液100 mg/kg, 同时每日灌胃蒸馏水100 μl/10 g;空白组及模型组小鼠每日灌胃等体积蒸馏水及每3日腹腔注射等体积0.9%NaCl溶液, 共给药60 d。采用Masson染色法评估各组小鼠子宫组织纤维化程度;采用免疫组化染色及Western blot法检测各组小鼠子宫组织中E-钙黏附蛋白(E-cadherin)、波形蛋白(Vimentin)、α-平滑肌肌动蛋白(α-SMA)、Yes相关蛋白(YAP)、锌指转录因子(Snail)表达情况。结果与模型组比较, 红藤方组Masson染色蓝染面积与总染色面积比值降低(P<0.05);免疫组化和Western blot检测显示, 与模型组比较, 红藤方组小鼠子宫组织E-cadherin表达升高(P<0.05), Vimentin、α-SMA、YAP表达降低(P<0.01或P<0.05)。结论红藤方可抑制ADS发生EMT、FMT, 从而抑制纤维化, 其作用机制与调控Hipoo/YAP通路相关。Objective To investigate the mechanism of Hongteng Decoction in inhibiting the adenomyosis(ADS)fibrosis by observing the effects on the key proteins of epithelial mesenchymal transformation(EMT),fibroblast-to-myofibroblast transformation(FMT)and Hippo pathway in uterine tissue of mice with ADS.Methods ICR mice were divided into blank group,model group,Hongteng Decoction group,and verteporfin group according to random number table method,with 8 mice in each group.The day of birth of the mice was day 0,and from day 1,mice in model group,Hongteng Decoction group and verteporfin group were given 1 mg/kg tamoxifen solvent for gavage for 5 days.On the 42nd day after molding,HE staining verified that the molding was successful.Starting from the 43rd day,mice in the Hongteng Decoction group were given TCM solution of Hongteng Decoction 16.5 g/kg everyday,and intraperitoneally injected with 0.9%NaCl solution(100μl/10 g)every 3 days.Mice in the verteporfin group were intraperitoneally injected with verteporfin solution of 100 mg/kg every 3 days,and intragastric with water of 100μl/10 g everyday.Mice in blank group and model group were intragastric with constant volume of water daily and intraperitoneally injected with 0.9%NaCl solution every 3 days.The drugs were administered for 60 days.The fibrosis degree of mice in each group was evaluated by Masson staining.The expressions of E-cadherin,Vimentin,α-SMA,YAP and Snail in uterine tissue of mice in each group were detected by immunohistochemistry and Western blot.Results Compared with the model group,the Masson staining expression in Hongteng Decoction group significantly decreased(P<0.05).Immunohistochemical and Western blot analysis showed that the expression of E-cadherin in uterine tissue of mice in Hongteng Decoction group significantly increased(P<0.05),while the expressions of Vimentin,α-SMA and YAP significantly decreased(P<0.01,P<0.05)compared with the model group.Conclusion Hongteng Decoction can inhibit the occurrence of EMT and FMT in ADS,thereby inhibiting

关 键 词：纤维化 子宫腺肌症 红藤方 Hippo信号通路 YAP-信号蛋白 小鼠 

分 类 号：R285.5[医药卫生—中药学]