红花水提物及羟基红花黄色素A 对原发性痛经寒凝血瘀证大鼠的 作用及机制研究

Objective To explore the pharmacological efiects and regulatory mechanisms of Carthami Flos water extract and its main constituent, hydroxysafilower yellow A ( HSYA), on primary dysmenorrhea rats with cold coagulation and blood stasis. Methods Forty-two female specific pathogen-free grade rats aged 6-8 weeks were divided into blank, model, HSYA( 0. 01 g/kg), ibuprofen( 0. 04 g/kg), and low (0.06 g/kg), medium (0.20 g/kg), and high (0.40 g/kg) Carthami Flos water extract dose groups using the random number table method, with six rats per group. A rat model was established using ice water bath stimulation combined with estradiol benzoate and oxytocin. Continuous gavage was administered for 6 days from the seventh day of modeling. After the intervention, the writhing reaction test was conducted. The rats, uteri, and ovaries were weighed to calculate the organ index. An enzyme-linked immunosorbent assay and radioimmunoassay were used to detect the prostaglandin E2 ( PGE2) and prostaglandin F2a ( PGF2a) contents in the uterus, thromboxane B2( TXB2 ) and 6 -keto-prostaglondin F1a ( 6-keto-PGF1a) in plasma, and estradiol (E2) in the serum. Hematoxylin and eosin staining were used to detect the pathological changes in uterine tissue. Immunohistochemistry was used to determine cyclooxygenase-2 ( COX - 2 ) expression in uterine tissue, whereas immunofluorescence was used to measure follicle-stimulating hormone receptor ( FSH-R) expression in ovarian tissue. Western blotting was used to detect gonadotropin-releasing hormone receptor ( GnRH-R) and FSH-R expression in uterine tissue. Results Compared with the blank group, the rats in the model group exhibited an increase in uterine and ovarian indices and increased PGE2 and PGF2a in the uterus. TXB2 in the plasma and E2 in the serum were also evaluated. Additionally, 6 -keto-PGF1a decreased, and COX - 2, GnRH-R, and FSH-R expression in the uterus and FSH-R expression in the ovaries also increased ( P <0.05). The morphology of the uterine tissue was disordered. Compared with the model group, the low Carthami Flos water extract dose group showed a decrease in uterine index ( P < 0. 05 ) . In the medium and high Carthami Flos water extract dose groups, the writhing response decreased, as did the uterine and ovarian indices and PGE2 and TXB2 contents. The 6 - keto-PGF1a content increased, whereas the GnRH-R protein expression in the uterus decreased ( P<0. 05). The high Carthami Flos water extract dose group also showed a decrease in PGF2a and FSH-R protein expression in the uterus (P<0. 05). In the HSYA group, the writhing response decreased, the uterine and ovarian indices decreased, the PGE2, PGF2a, and TXB2 contents decreased, and GnRH-R and FSH-R protein expression decreased in the uterus ( P< 0.05). The serum E2 levels of the groups that received Carthami Flos water extract at various doses and those of the HSYA group were reduced, and the uterine morphology was improved. COX-2 expression in the uterus and FSH-R protein expression in the ovaries were also reduced (P <0.05). Conclusion Carthami Flos water extract and HSYA can improve the pathological state of primary dysmenorrhea rats with cold coagulation and blood stasis. Its mechanism may be related to regulating the hypothalamic-pituitary-ovary axis. [ABSTRACT FROM AUTHOR]