Influence Of Gestrinone Combined With Letrozole On The Expression Of VEGF And MMP-9 In Endometriotic Lesions In Rats

BackgroundEndometriosis(EMs)is a common disease in gynecology,it is a benign disease,but it has the biological characteristics of malignant tumors.The pathogenesis of EMs is complicated,and no matter which theory has its limitations.People had gradually realized that cell apoptosis and angiogenesis play an important role in the occurrence of EMs in recent years.In the process of angiogenesis,vascular endothelial growth factor(Vascular endothelial growth factor,VEGF)is an important regulatory factor;matrix metal proteinase 9(MMP-9)also plays a certain role at the same time,which can promote blood vessels,induces angiogenesis and ultimately leads to the occurrence of EMs.Gestrinone can bind to the corresponding receptors on the intima,causing intimal atrophy,or even decidualization,and ultimately leading to necrosis and absorption of the lesion to achieve the purpose of treatment,but it cann’t solve the problem of the high recurrence rate of EMs.EMs is an estrogen-dependent disease,Letrozole inhibits the synthesis of estrogen by inhibiting aromatase activity,thereby playing a role in the treatment of estrogen-dependent tumors.Therefore,this study mainly explored the influence of gestrinone combined with letrozole on the expression of VEGF and MMP-9 in endometriotic lesions in rats.ObjectiveTo explore the influence of gestrinone combined with letrozole on VEGF and MMP-9in ectopic endometrial tissue of EMs model rats,compared with the two separate treatments,a control group was set up at the same time,the changes in the expression of VEGF and MMP-9 in the ectopic endometrial tissue of EMs model rats of gestrinone combined with letrozole and the two separately were observed,to provide a new idea and method for EMs treatment in clinic.MethodsThe establishment of EMs rat model adopts the endometrial autologous transplantation method,the successfully modeled rats were randomly divided into control group,gestrinone group,letrozole group and combination group,15 rats in each group.Calculate the actual dose of each group of rats according to the rat dose conversion formula in “Pharmacological Experimental Methodology”.The gestrinone capsules and letrozole tablets were crushed and added to peanut oil to form a 1 mg/m L suspension.In the gestrinone group,gavage was given at 0.26 mg/(kg·d)of gestrinone,the first gavage was given on the 1st day of each week,and the second gavage was given on the 4th day,twice a week,than gived the same amount of peanut oil to the stomach on the second,third,fifth,sixth,and seventh day of the week,for 4 consecutive weeks;The letrozole group was given letrozole 0.26 mg/(kg·d)daily by gavage for 4 consecutive weeks;The combination group was given gestrinone and letrozole for treatment,and the usage and dosage of gestrinone and letrozole were both no change,that is,letrozole daily by gavage using 0.26mg/(kg·d)dose;at the same time,combined with gestrinone by gavage on the 1st and 4th day of each week,twice a week,the gestrinone dose was still 0.26 mg/(kg·d),and the gavage was continued for 4 weeks;The control group was gavage the same amount of peanut oil every day,all were gavage for 4 weeks,than put them death,the ectopic diseased tissues were taken after laparotomy.The volume of ectopic lesions,expression of VEGF protein,MMP-9 protein and VEGF mRNA,MMP-9 mRNA in the ectopic endometrial tissue after treatment of the 4 groups were compared.Results1.The volume of ectopic lesions after treatment in the gestrinone group,letrozole group and the combination group was smaller than that of the control group,and the combined group was significantly smaller than the other two groups(P<0.05).2.The optical microscope showed that the positive expression ratio of cells after treatment in the gestrinone group,letrozole group and combination group was greatly reduced.3.The mean optical density(MOD)values of VEGF and MMP-9 protein after treatment in the ectopic endometrial tissue of rats in the gestrinone group,letrozole group and combination group was lower than those in the control group,and the combined group was significantly smaller than the other two groups(P<0.05).4.The expression intensity of VEGF mRNA and MMP-9 mRNA relative to β-actin after treatment in the ectopic endometrial tissue of rats in the gestrinone group,letrozole group and combination group was lower than those in the control group,and the combined group was significantly smaller than the other two groups(P<0.05).5.The pearson correlation analysis showed that the expression of VEGF and MMP-9in the ectopic endometrial tissue of EMs rats was positively correlated(P<0.05).Conclusion1.Both gestrinone and letrozole can down-regulate the expression of VEGF,MMP-9protein and VEGF mRNA,MMP-9 mRNA in ectopic endometrial tissue of EMs model rats,and reduce the volume of ectopic lesions,but effect of combined the two is more obvious.2.There is a certain positive correlation between the expression of VEGF and MMP-9in ectopic endometrial tissue of EMs rats.