OBJECTIVETo study the effects and mechanisms of Zuoguiyin (ZGY) on the ovarian nitric oxide (NO) production in peri-menopausal rats.

METHODSThe peri-menopausal model rats were respectively administered with low (13.78 g/kg), middle (20.67 g/kg), and high (31.00 g/kg) dose ZGY, and nilestriol for 8 weeks. Normal saline was given by gastrogavage to rats in the model group and the young control group (as the control group). The ovarian NO content and the activity of total nitric oxide synthase (NOS) were detected using nitrate reductase method and chemical colorimetry respectively. The mRNA and protein expressions of inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) were detected using RT-PCR and immunohistochemical assay.

RESULTS(1) Compared with that in the control group, the ovarian NO content and the activity of total NOS in peri-menopausal rats were significantly lower (P < 0.01). Middle and high dose ZGY could obviously up-regulate them (P < 0.01, P < 0.05). (2) The three kinds of NOS expression levels in perimenopausal rats were obviously lower when compared with those of the control group (P < 0.01). Middle dose ZGY could significantly promote all the three kinds of NOS expression levels of pre-senile rats (P < 0.01). High dose ZGY could up-regulate the expressions of iNOS and eNOS, while low dose ZGY could only enhance the iNOS expression (P < 0.01).

CONCLUSIONSThe down-regulated expressions of eNOS, iNOS, and nNOS in local ovaries resulted in decreased NOS activity and NO production, which were closely correlated with damaged microcirculatory vascular functions of ovaries in peri-menopausal rats. ZGY could protect rats' ovarian microcirculation by up-regulating the expressions of eNOS, iNOS, and nNOS, and enhancing the ovarian NOS activity and NO production.