Effect of PAMAM-mediated endostatin gene therapy on human endometriosis in nude mice

Objective To explore the effect of endostatin(ES) gene therapy mediated by polyamidoamine(PAMAM) on human endometriosis in nude mice.Methods One hundred and twenty nude female BALB/c mice were subcutaneously transplanted with human endometrium fragments for the establishment of endometriosis model.They were divided into four treatment groups: ES transfection group(n=33,a mixture of 65μg PAMAM and 20μg ES gene was injected into the lesion of nude mice);PAMAM group(n=30,a mixture of 65μg PAMAM and 20μg sterile saline was injected into the lesion of nude mice);normal saline group(n=27,85μl sterile saline was injected into the lesion of nude mice);blank group(n=30,nothing was injected).Each group was then divided into 2 subgroups,i.e.day 1 treatment and day 14 treatment subgroups.All nude mice were sacrificed 1 week after treatment.Ovaries and uterus were weighed,number of ovarian follicles was obtained,and ES,VEGF protein and MVD in nude mice were analyzed by immunohistochemistry.Results The ES expression was significantly higher in day 1 subgroup of ES transfection group than in the day 1 subgroups of other three groups(P0.05),while no significant differences were found in lesion weight,VEGF expression and MVD when comparing the day 1 subgroups of the 4 groups(P0.05).The ES expression was higher,VEGF expression was lower,MVD was less,and the volume of lesions was smaller and weight was lighter in the day 14 subgroup of ES transfection group than those in the day 14 subgroups of other three groups(P0.05).The VEGF expression was lower and MVD was less in day 1 subgroups than in day 14 subgroups(P0.05).No pathological change was observed in heart,liver,kidney,ovaries and uterus in nude mice of all the 4 groups;and also,no significant difference existed in reproductive organ weight and ovarian follicle number among the 4 groups(P0.05).Conclusion PAMAM-mediated endostatin gene therapy is effective for endometriosis given 14 days after model establishment,without producing side effect on heart,liver,kidney and reproductive organ in nude mice.