地诺孕素通过MMP-2/RhoA/ROCK信号通路对子宫内膜异位症病理及性激素水平的研究OA

Objective To explore the molecular mechanisms through which dienogest(DG)impacts pathology and serum sex hormone levels in a rat model of endometriosis(EM).Methods Adult female Sprague-Dawley rats were selected to establish EM models by autologous endometrial transplantation.The rats were divided into control group,model group,low-dose experimental group(intraperitoneal injection of DG at 1 mg·kg-1·d-1)and high-dose experimental group(intraperitoneal injection of DG at 2 mg·kg-1·d-1),with 10 rats in each group.Western blot was used to detect the protein levels of Ras homolog gene family member A(RhoA),Rho-associated coiled-coil containing protein kinase 1(ROCK1),ROCK2,matrix metalloproteinase-2(MMP-2),estrogen receptor(ER)and progesterone receptor(PR).Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)was applied to detect the expression of genes related to RhoA,ROCK1,ROCK2 and MMP-2.Enzyme-linked immunosorbent assay(ELISA)was adopted to measure the serum levels of estradiol(E2),progesterone(P),follicle-stimulating hormone(FSH)and luteinizing hormone(LH).Hematoxylin-eosin(HE)staining combined with histopathological scoring was performed to observe the histopathological morphology.Results The relative expression levels of RhoA protein in control group,model group,low-dose experimental group and high-dose experimental group were 0.49±0.05,1.25±0.11,0.42±0.03 and 0.39±0.02,respectively;the relative expression levels of ROCK1 protein were 0.37±0.08,0.67±0.08,0.52±0.10 and 0.35±0.05,respectively;the relative expression levels of ROCK2 protein were 0.70±0.09,1.45±0.12,0.54±0.10 and 0.45±0.03,respectively;the relative expression levels of MMP-2 protein were 0.43±0.08,1.07±0.15,0.40±0.07 and 0.24±0.08,respectively;the relative expression levels of ER protein were 0.63±0.08,1.02±0.09,0.48±0.05 and 0.40±0.06,respectively;the relative expression levels of PR protein were 0.46±0.04,1.23±0.10,0.27±0.05 and 0.21±0.03,respectively;the E2 levels were(51.23±5.16),(83.56±8.03),(65.33±6.15)and(58.72±5.47)pg·mL-1,respectively;the P levels were(10.55±1.20),(7.24±0.89),(8.81±1.02)and(9.50±1.11)ng·mL-1,respectively;the FSH levels were(5.22±0.87),(8.56±1.05),(7.03±0.69)and(6.21±0.64)mIU·ml-1,respectively;the LH levels were(4.83±0.72),(7.78±0.49),(6.29±0.58)and(5.55±0.74)mIU·mL-1,respectively.Compared with control group,model group showed statistically significant differences in all the above indicators,and statistically significant differences were also observed between low-dose and high-dose experimental groups with model group(all P＜0.05).Histopathological scores revealed severe pathological damage in the model group,which was alleviated after DG treatment in a dose-dependent manner.Hematoxylin-eosin(HE)staining results also indicated an improvement in cellular pathological changes.Conclusion DG shows therapeutic efficacy in EM rats by regulating the expression of related proteins and genes,affecting the serum sex hormone levels,and improving histopathological damage.The high-dose expreiment group has a particularly significant effect,which may offer a theoretical basis and new insights for the treatment of EM.