Establishment of a rabbit model of iatrogenic premature ovarian insufficiency
Objective To compare the effects of different doses of cyclophosphamide on ovarian function in New Zealand white rab-bits,and to explore the best administration regimen for the establishment of chemotherapy-induced premature ovarian insufficiency(POI)rabbit model.Methods Thirty-two ordinary female unmated New Zealand white rabbits were randomly divided into 4 groups with 8 rabbits in each group.Group A was the normal control group.Group B was intraperitoneally injected with 50 mg/kg cyclophos-phamide for 1 day and 8 mg/kg for 14 days.Group C received 50 mg/kg continuous intraperitoneal injection of cyclophosphamide for 3 days.Group D received 100 mg/kg continuous intraperitoneal injection of cyclophosphamide for 3 days.The status,body weight,ovar-ian length and ovarian index of rabbits in 4 groups were compared.The serum levels of estradiol and follicle-stimulating hormone were detected in 4 groups.HE staining was used to observe the ovarian tissue morphology,the number of follicles at all levels and the pro-portion of atretic follicles.The expression levels of apoptosis-related proteins Bax and Bcl2 in ovarian tissue of 4 groups were detected.Results Compared with group A,the expression of Bax protein in groups B,C and D was up-regulated(P<0.05),and the expression of Bcl2 protein was down-regulated(P<0.05).The number of primary and primary follicles in group B was less than that in group A,and the number of atretic follicles was more than that in group A,and the difference was statistically significant(P<0.05).After 3 weeksof intraperitoneal injection of cyclophosphamide,the body mass of rabbits in groups C and D was lower than that in group A,the length diameter of the ovary was shorter than that in group A,the ovarian index was lower than that in group A,the level of estradiol was lower than that in group A,the level of follicle stimulating hormone was higher than that in group A,the number of primary folli-cles,primary follicles,secondary follicles and sinus follicles was lower than that in group A,the number of atretic follicles was higher than that in group A,and the proportion of atretic follicles was higher,the difference was statistically significant(P<0.05).Two rab-bits in group D died after 5 days of administration.Compared with group A,there were no significant differences in body weight,ovarian length diameter,ovarian index,hormone level and number of follicles in group B,suggesting that the damage to the ovary was mild and not suitable for modeling.Compared with group A,there were statistically significant differences in body mass,ovarian length,ovarian index,hormone level and number of follicles at all levels of rabbits in group C and group D,but the ovarian damage in group D was se-vere and the rabbit tolerance was poor,two of them died after 5 days of administration,which was not suitable for modeling for follow-up studies.Conclusion 50 mg/kg continuous intraperitoneal injection of cyclophosphamide for 3 days is the best concentration to es-tablish a rabbit model of chemotherapy-damaged POI.This method is simple and easy to use,has stable ovarian injury and good toler-ance in animals,and can be used to evaluate the prognostic effect of different treatment schemes for POI,providing theoretical support for clinical research.
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NSTL
万方数据
维普
