基于COX-2/PGE2与VEGF/MVD通路探讨暖宫止痛贴治疗寒凝血瘀型原发性痛经的作用机制OA

Objective:To investigate the mechanism of action of Nuangong Zhitong plaster(NGZT)on rats with prima-ry dysmenorrhea(PD)of cold-congealed blood stasis type.Methods:The rat cold-congealed blood stasis syndrome was established by ice-water bath combined with epinephrine hydrochloride,estradiol benzoate combined with oxytocin to prepare a rat cold-congealed blood stasis type PD.Ibuprofen was used as the positive control,the number of writhing movements and latency time in rats were observed;serum levels of Prostaglandin E2(PGE2)and Prostaglandin F2α(PGF2α)were detected by Enzyme-Linked Immunosorbent Assay(ELISA);uterine morphology was observed by He-matoxylin-Eosin(HE)staining;microvessel density(MVD)was detected by immunofluorescence;protein and mRNA expression of PI3K/AKT/COX-2/VEGF pathway in uterine tissue was detected by Western blot and RT-PCR.Re-sults:NGZT significantly reduced the number of writhing movements and prolonged the latency time of writhing move-ments(P<0.01),elevated the levels of PGE2,lowered the levels of PGF2α inserum,and decreased PGF2α/PGE2 ratio,reduced the degree of edema and inflammatory infiltration in uterus,and downregulated protein and gene expression of COX-2,VEGF and MVD(P<0.01).The effect was comparable to that of ibuprofen,but no significant effect was ob-served on the PI3K/AKT pathway(P>0.05).Conclusion:The mechanism by which NGZT effectively improved cold-congealed blood stasis type PD in rat maybe inhibiting the COX-2/PGE2 inflammation pathway and the VEGF/MVD angiogenesis pathway,independently of the PI3K/AKT signalling pathway.