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山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (9): 148-154.doi: 10.6040/j.issn.1671-7554.0.2021.0865

• 科研论著 • 上一篇    

U0126对子宫内膜异位症大鼠MEK/ERK/NF-κB通路及增殖侵袭的影响

王芳1,陈华2,商丽红1,李茹月1,李咏梅1,杨玉娥1,哈春芳2,3   

  • 发布日期:2021-10-15
  • 通讯作者: 哈春芳. E-mail:hachunfang@163.com
  • 基金资助:
    国家自然科学基金(81660251);宁夏自然科学基金(2021AAC03414);宁夏医科大学2020年大学生创业创新计划

Effects of U0126 on MEK/ERK/NF-κB pathway, proliferation and invasion in rats with endometriosis

WANG Fang1, CHEN Hua2, SHANG Lihong1, LI Ruyue1, LI Yongmei1, YANG Yu,e1, HA Chunfang2, 3   

  1. 1. Clinical College of Ningxia Medical University, Yinchuan 750004, Ningxia, China;
    2. Gynecology Department, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China;
    3. Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Yinchuan 750004, Ningxia, China
  • Published:2021-10-15

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摘要： 目的 探讨丝裂原活化蛋白激酶抑制剂U0126对子宫内膜异位症大鼠丝裂原活化蛋白激酶/细胞外信号调节激酶蛋白(MEK/ERK)通路及增殖侵袭的影响。 方法 采用自体移植法建立子宫内膜异位症大鼠模型,造模成功的18只雌性SD大鼠随机分为模型组、二甲基亚砜(DMSO组)和U0126组(20 mg/kg),每组6只。另设假手术组6只作为对照组。用药4周后统一处死大鼠,测量并计算各组子宫内膜异位病灶体积,采用苏木精-伊红染色法观察各组大鼠内膜组织病理学形态变化,采用免疫组织化学染色法检测各组大鼠内膜组织中增殖细胞核抗原(PCNA)和基质金属蛋白酶9(MMP9)蛋白表达,采用Western blotting法检测各组大鼠内膜组织中MEK、ERK及NF-κB蛋白表达。 结果 与模型组相比,U0126组异位病灶体积明显缩小(F=4.54,P=0.02);苏木精-伊红染色结果显示,对照组在位内膜组织见子宫内膜腺上皮呈柱状排列,腺体排列整齐,腺腔完整,腺体周围未见出血及炎性细胞形成;与对照组相比,模型组及DMSO组在位内膜组织显示多个大小不等的子宫内膜异位腺体囊肿及间质反应,可见多量炎性细胞浸润,腺体周围可见出血及新生血管生成;与模型组相比,U0126组见子宫内膜腺体明显减少,腺腔变小,腺上皮变薄,间质反应减轻;免疫组化结果显示,与对照组相比,模型组及DMSO组在位内膜组织中PCNA和MMP9蛋白表达水平均升高(P<0.05);与模型组相比,U0126组PCNA和MMP9蛋白表达水平明显降低(P<0.05),DMSO组差异无统计学意义(P>0.05)。Western blotting结果显示,与对照组相比,模型组和DMSO组在位内膜组织中MEK、ERK、NF-κB蛋白表达均明显升高(P<0.05);与模型组相比,U0126组MEK、ERK、NF-κB蛋白表达均明显降低(P<0.05),DMSO组差异无统计学意义(P>0.05)。 结论 U0126可以明显抑制子宫内膜异位症大鼠异位病灶生长及腺体增生,其机制可能与抑制MEK/ERK/NF-κB通路活性降低在位内膜组织增殖侵袭能力有关。

关键词: 丝裂原活化蛋白激酶/细胞外蛋白调节激酶信号通路, 核转录因子, 增殖细胞核抗原, 基质金属蛋白酶9

Abstract: Objective To investigate the effects of U0126 on MEK/ERK/NF-κB pathway, proliferation and invasion in rats with endometriosis. Methods After autologous transplantation of endometriosis rat models were successfully established, 18 female SD rats were randomly divided into the model group, dimethyl sulfoxide(DMSO)group, U0126 group(20 mg/kg), and control group(sham operation group), with 6 rats in each group. The rats were sacrificed after 4 weeks of medication. The volume of endometriosis lesions were measured and calculated. HE staining was used to observe the pathological changes of the endometrium. Immunohistochemical staining and Western blotting were used to detect the expressions of proliferating cell nuclear antigen(PCNA), matrix metalloproteinase 9(MMP9), MEK, ERK and NF-κB in the eutopic endometrial tissues. Results Compared with the model group, U0126 group had significantly reduced volume of ectopic lesions(F=4.54, P=0.02). HE staining results showed that in the control group, the endometrial glandular epithelium was arranged in columns, the gland cavity was intact and neatly arranged, and there was no bleeding or inflammatory cell formation around the glands. The model group and DMSO group showed multiple endometriotic gland cysts and interstitial reactions of varying sizes, with a large amount of inflammatory cell infiltration, bleeding and new growth around the glands and angiogenesis. Compared with the model group, U0126 group had significantly smaller endometrial glands and glandular cavity, thinner glandular epithelium, and less interstitial reaction. The results of immunohistochemistry showed that compared with the control group, model group and DMSO group had significantly increased expressions of PCNA and MMP9 in the eutopic endometrial tissues (P<0.05); compared with the model group, U0126 group had significantly reduced protein expression of PCNA and MMP9(P<0.05). There were no statistically significant differences in the DMSO group(P>0.05). Western blotting indicated that compared with the control group, model group and DMSO group had significantly increased expressions of MEK, ERK and NF-κB in the eutopic endometrial tissues(P<0.05); Compared with the model group, U0126 group had significantly reduced expressions of MEK, ERK and NF-κB(P<0.05), while there were no significant differences in the DMSO group(P>0.05). Conclusion U0126 can significantly inhibit the growth of ectopic lesions and glandular hyperplasia in endometriosis rats, and the mechanism may be related to the inhibition of MEK/ERK/NF-κB pathway to reduce the proliferation and invasion of eutopic endometrial tissues.

Key words: MEK/ERK signaling pathway, Nuclear transcription factor κB, Proliferating cell nuclear antigen, Matrix metalloproteinase 9

中图分类号: 

  • R711.71
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