Expression And Significance Of Transcription Factor Nrf2 Mediated By Antioxidant Enzymes MnSOD And GPX1 In Uterine Ligament Tissue Of Pelvic Organ Prolapse

Objective:In this study,we studied the expression of antioxidant enzymes MnSOD,GPX1 and transcription factor Nrf2 in uterine ligament tissue of pelvic organ prolapse(POP),and further explored whether Keap1-Nrf2/ARE antioxidant pathway played a certain role in the occurrence and development of POP.At the same time,we analyzed the relevant factors affecting the mechanism of oxidative stress of POP,so as to provide new targets and ideas for the treatment of POP.Methods:In this study,22 patients with POP(III-IV)treated in the Department of Obstetrics and Gynecology of the second Hospital of Shanxi Medical University from October 2018 to December 2019 were selected as the POP group,which were operated by laparoscopic hysterectomy plus vaginal sacral fixation,and 26 non-POP patients hospitalized in the gynecology and obstetrics department of Shanxi Medical University in the same period were selected as the control group.All patients had no history of systemic hormone use in the past 3 months,no history of urinary incontinence or vaginal pelvic floor surgery,and no history of malignant tumor,hormone-related disease,diabetes,asthma or cardiovascular disease.After the approval of the ethics discussion group and the consent of the patients,the corresponding tissue samples were taken during the operation.The tissue of the main ligament was taken about 1.0cm below the uterine artery,and the sacral ligament was taken about 1.0cm beyond the junction between the ligament and thecervix.The histological characteristics of ligament were observed by HE staining and special staining(Masson staining and aldehyde-fuchsin staining),the expression of MnSOD and GPX1 was detected by immunohistochemistry,and the expression of MnSOD,GPX1 and Nrf2 was detected by western blotting(western blot,WB)at molecular level.Results:1.The results of HE and special staining in each group showed that a large number of fibrous connective tissue could be seen in the main uterine ligament and sacral ligament in the control group,mainly collagen and elastic fibers,with dense and orderly tissue structure,while in the POP group,the fibrous connective tissue in the uterine ligament was significantly reduced,and the structure was loose and disordered,in which there were fine fragmentation and rupture of collagen and elastic fibers and increase of adipose tissue.2.The results of immunohistochemical staining showed that both MnSOD and GPX1 were mainly expressed in the cytoplasm,and the expression of MnSOD and GPX1 in the main uterine ligament and sacral ligament in the POP group was significantly lower than that in the control group(P<0.05),and there was a positive correlation between them(P<0.01).3.The results of WB detection showed that the expression levels of antioxidant enzymes MnSOD,GPX1 and transcription factor Nrf2 in uterine main ligament and sacral ligament in POP group were significantly lower than those in control group(P<0.05),and they were positively correlated with the expression of Nrf2(P<0.01).The expression level of GPX1 was negatively correlated with age and parity in POP group(P<0.01),but not with pregnancy and BMI.Conclusion:1.The mechanism of oxidative stress is closely related to the occurrence anddevelopment of POP.2.Transcription factor Nrf2 may be involved in the regulation of oxidative stress in POP through Keap1-Nrf2/ARE antioxidant pathway.3.Age and parity are the risk factors of POP oxidative stress damage.