Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (9): 148-154.doi: 10.6040/j.issn.1671-7554.0.2021.0865

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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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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

CLC Number: 

  • R711.71
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