紫草素通过调节ERK信号通路对子宫肌瘤大鼠的影响  

Shikonin Affects Uterine Leiomyoma in Rats by Regulating ERK Signaling Pathway

作　　者：王芳芳 燕飞虎 李伟 王燕 况鹏娟 WANG Fang-fang;YAN Fei-hu;LI Wei;WANG Yan;KUANG Peng-juan(Hainan Tumor Hospital,Haikou570100,China)

机构地区：[1]海南省肿瘤医院,海口570100

出　　处：《中国实验方剂学杂志》2021年第21期131-137,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：海南省自然科学基金项目(813265)。

摘　　要：目的:探讨紫草素对子宫肌瘤大鼠的作用及其分子机制。方法:SPF级别SD大鼠60只,雌性,体质量200~250 g,随机分为空白组、模型组、紫草素低、中、高剂量组(5,10,20 mg·kg^(-1))和米非司酮组;建立子宫肌瘤大鼠模型,连续给药4周后检测子宫湿重、子宫系数和平滑肌厚度的变化;采用苏木素-伊红(HE)染色观察子宫组织的病理染色变化;采用酶联免疫吸附测定试验(ELISA)检测血清和子宫中雌激素受体(ER)和孕激素受体(PR)的含量;蛋白免疫印迹法(Western blot)检测子宫组织中ER,PR,磷酸化细胞外调节激酶(p-ERK)和ERK的蛋白水平。结果:与空白组比较,模型组大鼠的子宫湿重、子宫系数和平滑肌厚度显著升高(P<0.01);子宫发生畸变,平滑肌细胞局灶性坏死和增生,且伴有中性粒细胞浸润等病理变化;血清ER和PR含量显著升高(P<0.01);子宫组织ER,PR和p-ERK的蛋白表达升高(P<0.01)。与模型组比较,紫草素中剂量组、高剂量组和米非司酮组大鼠的子宫湿重、子宫系数和平滑肌厚度显著降低(P<0.01);子宫病理变化缓解,且血清ER和PR含量降低,子宫组织ER,PR和p-ERK的蛋白表达降低,差异具有统计学意义(P<0.05)。紫草素低剂量组较模型组大鼠子宫湿重、平滑肌层厚度、血清中ER水平,子宫组织PR和p-ERK蛋白表达水平明显降低,差异具有统计学意义(P<0.05,P<0.01)。结论:紫草素可能通过抑制ERK信号活化,从而产生抗子宫肌瘤活性。Objective:To investigate the effect of shikonin on uterine leiomyoma in rats and its molecular mechanism.Method:Sixty female SD rats,of SPF grade and weighing 200-250 g,were randomly divided into the control group,model group,low-,medium-,and high-dose(5,10,20 mg·kg^(-1))shikonin groups,and mifepristone group.A rat model of uterine leiomyoma was established,and the changes in uterine wet weight,uterine coefficient,and smooth muscle thickness were detected after drug administration for four successive weeks.The pathological changes in uterine tissue were observed by hematoxylin-eosin(HE)staining.The contents of estrogen receptor(ER)and progesterone receptor(PR)in serum and uterus were measured by enzyme-linked immunosorbent assay(ELISA),and the protein expression levels of ER,PR,phosphorylated extracellular signal-regulated kinase(p-ERK),and ERK in the uterine tissue were assayed by Western blot.Result:Compared with the control group,the model group exhibited significantly increased uterine wet weight,uterine coefficient,and smooth muscle thickness(P<0.01),uterus deformity,focal smooth muscle cell necrosis and hyperplasia,neutrophil infiltration.elevated serum and uterine ER and PR(P<0.01),and up-regulated p-ERK protein expression in the uterine tissue(P<0.01).Compared with the model group,shikonin at the middle and high doses and mifepristone significantly reduced the uterine wet weight,uterine coefficient,and smooth muscle thickness(P<0.01),relieved the pathological changes in uterus,and lowered serum and uterine ER and PR,and down-regulated the p-ERK protein expression in the uterine tissue(P<0.05).In addition,the uterine wet weight,smooth muscle thickness,serum ER,and uterine PR and p-ERK protein expression in the low-dose shikonin group were significantly lower than those in the model group(P<0.05).Conclusion:Shikonin produces the anti-uterine leiomyoma activity possibly by inhibiting the activation of ERK pathway.

关 键 词：紫草素 子宫肌瘤 细胞外调节激酶(ERK)信号通路 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]