氧化小檗碱对子宫内膜异位症小鼠的影响及作用机制研究OA

Objective To construct the murine endometriosis model and explore the impact and mechanism of oxyberberine(OBB)in murine endometriosis.Methods Twenty-five female Kunming mice aged 6-8 weeks were randomly divided into a control group(n=7)and an EMs model group(n=18)using a random number table method.In the control group,1 mouse was used for verifying the modeling results,and 6 mice were used for subsequent experimental control;mice in the control group underwent sham surgery.In the EMs model group,endometriosis models were established by autologous endometrial transplantation,among which 2 mice were used to verify successful modeling,and the remaining 16 mice were further randomly divided into a model group(n=8)and a model+OBB intervention group(n=8).Two weeks and 4 weeks after OBB intervention in the model group,ectopic lesions in each group were assessed through hematoxylin-eosin(HE)staining and Masson's trichrome staining.After 4 weeks of intervention,proteins from the the peritoneum tissues of the control mice,ectopic lesions of the model mice,and ectopic lesions of mice in the model+OBB intervention group were extracted,and Western blot analysis was used to detect the expression levels of mitophagy-related proteins,including microtubule-associated protein 1 light chain 3β(LC3B)/microtubule-associated protein 1 light chain 3α(LC3A),cytochrome C oxidase subunit Ⅳ(COX Ⅳ),phosphorylated Parkin(p-Parkin),and Phosphatase and Tensin Homolog(PTEN)-induced putative kinase 1(PINK1).Results Compared with ectopic lesions of mice treated with OBB for 2 weeks,the volume of ectopic lesions after 4 weeks was significantly decreased.HE staining showed that lesions in the model group had gland-like morphology with dense epithelial cells,which might represent endometriotic lesions;such conditions were absent in the model+OBB intervention group.Masson's staining revealed that compared with the peritoneum tissues in the control group,the lesion tissues of mice in the model group had abundant collagen fibers with extremely irregular distribution,while collagen deposition was significantly less in the model+OBB intervention group.Compared with the control group,the model group showed downregulation of LC3B/A,p-Parkin,and PINK1 protein expression in the peritoneum tissues(all P＜0.05),and upregulation of COX Ⅳ protein expression(P＜0.05);In contrast,compared with the model group,the model+OBB intervention group showed upregulation of LC3B/A,p-Parkin,and PINK1 protein expression(all P＜0.05)and downregulation of COX Ⅳ protein expression(P＜0.05).Conclusion OBB acts on mice endometriosis by downregulating the protein expressions of LC3B/A,p-Parkin and PINK1,and upregulating COX Ⅳ protein expression.It inhibits the progression of endometriotic lesions by suppressing mitophagy.