Lichong decoction inhibits micro-angiogenesis by reducing the expressions of hypoxia inducible factor-1αand vascular endothelial growth factor in hysteromyoma mouse model

OBJECTIVE:To investigate the efficacy of Lichong decoction(LD)from Traditional Chinese Medicine,on micro-angiogenesis in a mouse model of hysteromyoma.METHODS:A mouse model of hysteromyoma was developed by orthotopic intrauterine injection of primary human myoma cells isolated from patients from the Beijing Obstetrics and Gynecology Hospital into CB-17 Scid mice.Mice were administered high-dose LD,low-dose LD,mifepristone or water(control)daily by gavage for 4 weeks.Uterine diameter and coefficient(uterine weight/body weight)were measured.Uterine morphology was assessed by light microscopy(hematoxylin and eosin)and transmission electron microscopy.Serum levels of estradiol,progesterone,follicle-stimulating hormone and luteinizing hormone(LH)were measured by enzyme-linked immunosorbent assay.Uterine protein expression of hypoxia inducible factor(HIF)-1α,CD31 and proliferating cell nuclear antigen(PCNA)was detected by immunohistochemistry.VEGF and HIF-1αm RNAs were quantified by RT-PCR.RESULTS:High-dose LD,low-dose LD and mifepristone reduced uterine diameter and coefficient,and attenuated the morphologic abnormalities associated with hysteromyoma.High-dose LD,low-dose LD and mifepristone inhibited hysteromyoma-induced micro-angiogenesis,as evidenced by a decrease in the number of new microvessels co-immunostaining for CD31 and PCNA(P<0.01).High-dose LD and mifepristone lowered serum levels of estradiol,progesterone and LH(P<0.05).High-dose LD,low-dose LD and mifepristone down-regulated HIF-1αm RNA and protein expressions and VEGF m RNA expression(P<0.01).CONCLUSION:The inhibition of hysteromyoma by LD may involve reductions in HIF-1αand VEGF expression and suppression of micro-angiogenesis.